Abstract
Among the intrapulmonary myelinated vagal sensory airway receptors, pulmonary neuroepithelial bodies (NEBs) definitely reveal the most complex organisation. This updated review aims at delivering the broad and thorough knowledge of the system that is essential for understanding its physiological relevance.
Complexly organised pulmonary NEBs are an integral part of the intrapulmonary airway epithelium of all air-breathing vertebrates. For decades, a quest has been going on to unravel the functional significance of these intriguing structures that appear to be modified in the course of many pulmonary diseases.
The pulmonary NEB microenvironment (ME) is composed of organoid clusters of pulmonary neuroendocrine cells (PNECs) that are able to store and release neurotransmitters and are closely contacted by extensive (mainly afferent) nerve terminals, emphasising a potential receptor/effector role and probable signalling to the central nervous system. PNECs are largely shielded from the airway lumen by a special type of Clara cells, the Clara-like cells, with potential stem cell characteristics.
Since pulmonary NEBs are widely dispersed in the airway epithelium, and represent less than one percent of the cells in the epithelial lining, investigating the NEB ME largely depends on its unequivocal microscopic identification. Nowadays, multidisciplinary approaches allow to combine functional morphological investigations in cryosections and cleared whole lungs, live cell imaging in lung vibratome slices, and selective gene expression analysis after laser microdissection of genetically tagged NEBs.
So far, functional studies of the pulmonary NEB ME revealed that PNECs can be activated by various mechanical and chemical stimuli, resulting in a calciummediated release of neurotransmitters. A number of publications in the past decades have exposed NEBs as potential hypoxia sensors.
In the past few years, combination of in vivo experiments and gene expression analysis unveiled the pulmonary NEB ME as a quiescent stem cell niche in healthy postnatal mouse lungs. The stem cell population was shown to be activated by transient mild inflammation, and silencing appears to involve bone morphogenetic protein signalling that may be mediated by vagal afferents.
Today, it is clear that only an integrated approach that takes all current information into account will be able to explain the full role of the pulmonary NEB ME in health and disease.
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References
Adriaensen D, Scheuermann DW (1993) Neuroendocrine cells and nerves of the lung. Anat Rec 236:70–85
Adriaensen D, Timmermans JP (2011) Breath-taking complexity of vagal C-fibre nociceptors: implications for inflammatory pulmonary disease, dyspnoea and cough. J Physiol 589:3–4
Adriaensen D, Timmermans J-P (2004) Purinergic signalling in the lung: important in asthma and COPD? Curr Opin Pharmacol 4:207–214
Adriaensen D, Gomi T, Scheuermann DW, Timmermans J-P, De Groodt-Lasseel MHA (1993) Abundance of serotonin-containing cells in the respiratory tract of a salamander, Cynops pyrrhogaster. Ann Anat:226–227
Adriaensen D, Scheuermann DW, Gajda M, Brouns I, Timmermans J-P (2001) Functional implications of extensive new data on the innervation of pulmonary neuroepithelial bodies. It J Anat Embryol 106:395–403
Adriaensen D, Brouns I, Van Genechten J, Timmermans J-P (2003) Functional morphology of pulmonary neuroepithelial bodies: extremely complex airway receptors. Anat Rec 270A:25–40
Adriaensen D, Brouns I, Pintelon I, De Proost I, Timmermans J-P (2006) Evidence for a role of neuroepithelial bodies as complex airway sensors: comparison with smooth muscle-associated airway receptors. J Appl Physiol 101:960–970
Agostoni E, Chinnock JE, De Daly MB, Murray JG (1957) Functional and histological studies of the vagus nerve and its branches to the heart, lungs and abdominal viscera in the cat. J Physiol 135:182–205
Aguayo SM (1993) Pulmonary neuroendocrine cells in tobacco-related lung disorders. Anat Rec 236:122–127
Aguayo SM (1994) Determinants of susceptibility to cigarette smoke. Potential roles for neuroendocrine cells and neuropeptides in airway inflammation, airway wall remodeling, and chronic airflow obstruction. Am J Respir Crit Care Med 149:1692–1698
Aguayo SM, King TE, Waldron JA, Sherritt KM, Kane MA (1990) Increased pulmonary neuroendocrine cells with bombesin-like immunoreactivity in adult patients with eosinophilic granuloma. J Clin Invest 86:838–844
Aguayo SM, Miller YE, Waldron JA, Bogin RM, Sunday ME, Staton GW, Beam WR, King TE (1992) Brief report: idiopathic diffuse hyperplasia of pulmonary neuroendocrine cells and airways disease. New Engl J Med 327:1285–1288
Akram KM, Yates LL, Mongey R, Rothery S, Gaboriau DCA, Sanderson J, Hind M, Griffiths M, Dean CH (2019) Live imaging of alveologenesis in precision-cut lung slices reveals dynamic epithelial cell behaviour. Nat Commun 10:1178
Alcaino C, Knutson KR, Treichel AJ, Yildiz G, Strege PR, Linden DR, Li JH, Leiter AB, Szurszewski JH, Farrugia G, Beyder A (2018) A population of gut epithelial enterochromaffin cells is mechanosensitive and requires Piezo2 to convert force into serotonin release. Proc Natl Acad Sci U S A 115:E7632–E7641
Allibone RO, Gosney JR (1990) Rapid changes in pulmonary endocrine cells in acute bronchopneumonic consolidation. J Pathol 161:347
Alm AS, Li K, Chen H, Wang D, Andersson R, Wang X (2010) Variation of lipopolysaccharide-induced acute lung injury in eight strains of mice. Respir Physiol Neurobiol 171:157–164
Asabe K, Tsuji K, Handa N, Kajiwara M, Suita S (1999) Immunohistochemical distribution of bombesin-positive pulmonary neuroendocrine cells in a congenital diaphragmatic hernia. Surg Today 29:407–412
Asselin-Labat ML, Filby CE (2012) Adult lung stem cells and their contribution to lung tumourigenesis. Open Biol 2:120094
Atanasova KR, Reznikov LR (2018) Neuropeptides in asthma, chronic obstructive pulmonary disease and cystic fibrosis. Respir Res 19:149
Attisano L, Wrana JL (2013) Signal integration in TGF-beta, WNT, and Hippo pathways. F1000prime Rep 5:17
Avadhanam KP, Plopper CG, Pinkerton KE (1997) Mapping the distribution of neuroepithelial bodies of the rat lung. A whole-mount immunohistochemical approach. Am J Pathol 150:851–859
Ball D (2004) Achaete–scute homolog-1 and Notch in lung neuroendocrine development and cancer. Cancer Lett 204:159–169
Barrios J, Patel KR, Aven L, Achey R, Minns MS, Lee Y, Trinkaus-Randall VE, Ai X (2017) Early life allergen-induced mucus overproduction requires augmented neural stimulation of pulmonary neuroendocrine cell secretion. FASEB J 31:4117–4128
Barrios J, Kho AT, Aven L, Mitchel JA, Park JA, Randell SH, Miller LA, Tantisira KG, Ai X (2019) Pulmonary neuroendocrine cells secrete gamma-aminobutyric acid to induce goblet cell hyperplasia in primate models. Am J Respir Cell Mol Biol 60:687–694
Basil MC, Katzen J, Engler AE, Guo M, Herriges MJ, Kathiriya JJ, Windmueller R, Ysasi AB, Zacharias WJ, Chapman HA, Kotton DN, Rock JR, Snoeck HW, Vunjak-Novakovic G, Whitsett JA, Morrisey EE (2020) The cellular and physiological basis for lung repair and regeneration: past, present, and future. Cell Stem Cell 26:482–502
Bayliss DA, Barret QB (2008) Emerging roles for two-pore-domain potassium channels and their potential therapeutic impact. Trends Pharmacol Sci 29:566–575
Becker KL, Silva OL (1981) Hypothesis: the bronchial Kulchitsky (K) cell as a source of humoral biologic activity. Med Hypotheses 7:943–949
Becker KL, Geelhoed G, O'Neill W, Monaghan KG, Snider RH, Moore CF, Silva OL (1980) Calcitonin in tissues of thyroidectomized monkey. Experientia 36:609–610
Beech DJ (2007) Canonical transient receptor potential 5. In: Flockerzi V, Nilius B (eds) Handbook of experimental pharmacology. Springer, pp 109–123
Bellusci S, Henderson R, Winnier G, Oikawa T, Hogan BL (1996) Evidence from normal expression and targeted misexpression that bone morphogenetic protein (Bmp-4) plays a role in mouse embryonic lung morphogenesis. Development 122:1693–1702
Bertoncello I, McQualter JL (2013) Lung stem cells: do they exist? Respirology 18:587–595
Bishop AE (2004) Pulmonary epithelial stem cells. Cell Prolif 37:89–96
Blaisdell CJ, Gail DB, Nabel EG (2009) National heart, lung, and blood institute perspective: lung progenitor and stem cells--gaps in knowledge and future opportunities. Stem Cells 27:2263–2270
Boers JE, denBrok JLM, Koudstaal J, Arends JW, Thunnissen FBJM (1996) Number and proliferation of neuroendocrine cells in normal human airway epithelium. Am J Respir Crit Care Med 154:758–763
Bollé T, Lauweryns JM, Van Lommel A (2000) Postnatal maturation of neuroepithelial bodies and carotid body innervation: a quantitative investigation in the rabbit. J Neurocytol 29:241–248
Borczuk AC (2020) Pulmonary Neuroendocrine Tumors. Surg Pathol Clin 13:35–55
Borges M, Linnoila RI, van de Velde HJ, Chen H, Nelkin BD, Mabry M, Baylin SB, Ball DW (1997) An achaete-scute homologue essential for neuroendocrine differentiation in the lung. Nature 386:852–855
Borok Z, Li C, Liebler J, Aghamohammadi N, Londhe VA, Minoo P (2006) Developmental pathways and specification of intrapulmonary stem cells. Pediatr Res 59:84R–93R
Bowman CL, Gottlieb PA, Suchyna TM, Murphy YK, Sachs F (2007) Mechanosensitive ion channels and the peptide inhibitor GsMTx-4: History, properties, mechanisms and pharmacology. Toxicon 49:249–270
Brain SD, Williams TJ, Tippins JR, Morris HR, MacIntyre I (1985) Calcitonin gene-related peptide is a potent vasodilator. Nature 313:54–56
Branchfield K, Nantie L, Verheyden JM, Sui P, Wienhold MD, Sun X (2016) Pulmonary neuroendocrine cells function as airway sensors to control lung immune response. Science 351:707–710
Brennan SC, Davies TS, Schepelmann M, Riccardi D (2014) Emerging roles of the extracellular calcium-sensing receptor in nutrient sensing: control of taste modulation and intestinal hormone secretion. Br J Nutr 111(Suppl 1):S16–S22
Brennan SC, Wilkinson WJ, Tseng HE, Finney B, Monk B, Dibble H, Quilliam S, Warburton D, Galietta LJ, Kemp PJ, Riccardi D (2016) The extracellular calcium-sensing receptor regulates human fetal lung development via CFTR. Sci Rep 6:21975
Breuer R, Zajicek G, Christensen TG, Lucey EC, Snider GL (1990) Cell kinetics of normal adult hamster bronchial epithelium in the steady state. Am J Respir Cell Mol Biol 2:51–58
Brouns I, Adriaensen D, Burnstock G, Timmermans J-P (2000) Intraepithelial vagal sensory nerve terminals in rat pulmonary neuroepithelial bodies express P2X3 receptors. Am J Respir Cell Mol Biol 23:52–61
Brouns I, Van Genechten J, Hayashi H, Gajda M, Gomi T, Burnstock G, Timmermans J-P, Adriaensen D (2003) Dual sensory innervation of pulmonary neuroepithelial bodies. Am J Respir Cell Mol Biol 28:275–285
Brouns I, Pintelon I, Van Genechten J, De Proost I, Timmermans J-P, Adriaensen D (2004) Vesicular glutamate transporter 2 is expressed in different nerve fibre populations that selectively contact pulmonary neuroepithelial bodies. Histochem Cell Biol 121:1–12
Brouns I, De Proost I, Pintelon I, Timmermans J-P, Adriaensen D (2006a) Sensory receptors in the airways: neurochemical coding of smooth muscle-associated airway receptors and pulmonary neuroepithelial body innervation. Auton Neurosci 126–127:307–319
Brouns I, Pintelon I, De Proost I, Alewaters R, Timmermans J-P, Adriaensen D (2006b) Neurochemical characterisation of sensory receptors in airway smooth muscle: comparison with pulmonary neuroepithelial bodies. Histochem Cell Biol 125:351–367
Brouns I, Oztay F, Pintelon I, De Proost I, Lembrechts R, Timmermans JP, Adriaensen D (2009a) Neurochemical pattern of the complex innervation of neuroepithelial bodies in mouse lungs. Histochem Cell Biol 131:55–74
Brouns I, Pintelon I, De Proost I, Timmermans J-P, Adriaensen D (2009b) Diverse and complex airway receptors in rodent lungs. In: Zaccone G, Cutz E, Adriaensen D, Nurse CA, Mauceri A (eds) Airway chemoreceptors in the vertebrates. Structure, evolution and function. Science Publishers, Enfield, New Hampshire, pp 235–268
Brouns I, Pintelon I, Timmermans JP, Adriaensen D (2012) Novel insights in the neurochemistry and function of pulmonary sensory receptors. Adv Anat Embryol Cell Biol 211(1–115):vii
Burnstock G (1999) Release of vasoactive substances from endothelial cells by shear stress and purinergic mechano-sensory transduction. J Anat 194:335–343
Burnstock G (2000) P2X receptors in sensory neurons. Br J Anaesth 84:476–788
Burnstock G (2001a) Expanding field of purinergic signaling. Drug Dev Res 52:1–10
Burnstock G (2001b) Purine-mediated signalling in pain and visceral perception. TiPS 22:182–188
Burnstock G (2001c) Purinergic signalling in the gut. In: Abbracchio MP, Williams M (eds) Purinergic and pyrimidinergic signalling II cardiovascular, respiratory, immune, metabolic and gastrointestinal tract function. Springer, Berlin, pp 141–238
Burnstock G (2006) Historical review: ATP as a neurotransmitter. Trends Pharmacol Sci 27:166–176
Burnstock G (2009) Purinergic mechanosensory transduction and visceral pain. Mol Pain 5:69
Burnstock G, Brouns I, Adriaensen D, Timmermans JP (2012) Purinergic signaling in the airways. Pharmacol Rev 64:834–868
Bystrova MF, Romanov RA, Rogachevskaja OA, Churbanov GD, Kolesnikov SS (2010) Functional expression of the extracellular-Ca2+-sensing receptor in mouse taste cells. J Cell Sci 123:972–982
Cabarcas SM, Mathews LA, Farrar WL (2011) The cancer stem cell niche—there goes the neighborhood? Int J Cancer 129:2315–2327
Cadieux A, Springall DR, Mulderry PK, Rodrigo J, Ghatei MA, Terenghi G, Bloom SR, Polak JM (1986) Occurrence, distribution and ontogeny of CGRP immunoreactivity in the rat lower respiratory tract: effect of capsaicin treatment and surgical denervations. Neuroscience 19:605–627
Campelo MRG, Curbera GA, Gallego GA, Pulido EG, Aparicio LMA (2011) Stem cell and lung cancer development: blaming the Wnt, Hh and Notch signalling pathway. Clin Transl Oncol 13:77–83
Canning BJ (2006) Reflex regulation of airway smooth muscle tone. J Appl Physiol 101:971–985
Carr MJ, Undem BJ (2003) Bronchopulmonary afferent nerves. Respirology 8:291–301
Cattaneo MG, Codignola A, Vicentini LM, Clementi F, Sher E (1993) Nicotine stimulates a serotonergic autocrine loop in human small-cell lung carcinoma. Cancer Res 53:5566–5568
Chang RB, Strochlic DE, Williams EK, Umans BD, Liberles SD (2015) Vagal sensory neuron subtypes that differentially control breathing. Cell 161:622–633
Chatterjee K, Kamimoto JJ, Dunn A, Mittadodla E, Joshi M (2016) A case of DIPNECH presenting as usual interstitial pneumonia. Pneumonol Alergol Pol 84:174–177
Chavez-Abiega S, Mos I, Centeno PP, Elajnaf T, Schlattl W, Ward DT, Goedhart J, Kallay E (2020) Sensing extracellular calcium—an insight into the structure and function of the calcium-sensing receptor (CaSR). Adv Exp Med Biol 1131:1031–1063
Chen F, Fine A (2016) Stem cells in lung injury and repair. Am J Pathol 186:2544–2550
Chow JY, Estrema C, Orneles T, Dong X, Barrett KE, Dong H (2011) Calcium-sensing receptor modulates extracellular Ca(2+) entry via TRPC-encoded receptor-operated channels in human aortic smooth muscle cells. Am J Physiol Cell Physiol 301:C461–C468
Chung MI, Bujnis M, Barkauskas CE, Kobayashi Y, Hogan BLM (2018) Niche-mediated BMP/SMAD signaling regulates lung alveolar stem cell proliferation and differentiation. Development:145
Coleridge HM, Coleridge JC (1994) Pulmonary reflexes: neural mechanisms of pulmonary defense. Annu Rev Physiol 56:69–91
Coleridge HM, Coleridge JC (1997) Afferent nerves in the airways. In: Barnes PJ (ed) Autonomic control of the respiratory system. Taylor & Francis, pp 39–58
Collins BJ, Kleeberger W, Ball DW (2004) Notch in lung development and lung cancer. Semin Cancer Biol 14:357–364
Conidi A, Cazzola S, Beets K, Coddens K, Collart C, Cornelis F, Cox L, Joke D, Dobreva MP, Dries R, Esguerra C, Francis A, Ibrahimi A, Kroes R, Lesage F, Maas E, Moya I, Pereira PN, Stappers E, Stryjewska A, van den Berghe V, Vermeire L, Verstappen G, Seuntjens E, Umans L, Zwijsen A, Huylebroeck D (2011) Few Smad proteins and many Smad-interacting proteins yield multiple functions and action modes in TGFbeta/BMP signaling in vivo. Cytokine Growth Factor Rev 22:287–300
Conigrave AD (2016) The calcium-sensing receptor and the parathyroid: past, present, future. Front Physiol 7:563
Conigrave AD, Ward DT (2013) Calcium-sensing receptor (CaSR): pharmacological properties and signaling pathways. Best Pract Res Clin Endocrinol Metab 27:315–331
Cook RM, Miller YE, Bunn PA Jr (1993) Small cell lung cancer: etiology, biology, clinical features, staging, and treatment. Curr Probl Cancer 17:69–141
Cornelissen W, Timmermans J-P, Van Bogaert P-P, Scheuermann DW (1996) Electrophysiology of porcine myenteric neurons revealed after vital staining of their cell bodies. A preliminary report. Neurogastroenterol Mot 8:101–109
Coste B, Mathur J, Schmidt M, Earley TJ, Ranade S, Petrus MJ, Dubin AE, Patapoutian A (2010) Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science 330:55–60
Cox CD, Bavi N, Martinac B (2017) Origin of the force: the force-from-lipids principle applied to piezo channels. Curr Top Membr 79:59–96
Cox CD, Bavi N, Martinac B (2019) Biophysical principles of ion-channel-mediated mechanosensory transduction. Cell Rep 29:1–12
Cox ML, Eddy SM, Stewart ZS, Kennel MR, Man MZ, Paulauskis JD, Dunstan RW (2008) Investigating fixative-induced changes in RNA quality and utility by microarray analysis. Exp Mol Pathol 84:156–172
Cunningham JT, Wachtel RE, Abboud FM (1995) Mechanosensitive currents in putative aortic baroreceptor neurons in vitro. J Neurophysiol 73:2094–2098
Cutz E (1997) Studies on neuroepithelial bodies under experimental and disease conditions. In: Cutz E (ed) Cellular and molecular biology of airway chemoreceptors. Landes Bioscience, Austin, pp 109–129
Cutz E (2015) Hyperplasia of pulmonary neuroendocrine cells in infancy and childhood. Semin Diagn Pathol 32:420–437
Cutz E, Jackson A (1999) Neuroepithelial bodies as airway oxygen sensors. Respir Physiol 115:201–214
Cutz E, Chan W, Wong V, Conen PE (1974) Endocrine cells in rat fetal lungs. Ultrastructural and histochemical study. Lab Invest 30:458–464
Cutz E, Chan W, Sonstegard KS (1978a) Identification of neuro-epithelial bodies in rabbit fetal lungs by scanning electron microscopy: a correlative light, transmission and scanning electron microscopic study. Anat Rec 192:459–466
Cutz E, Sonstegard KS, Chan W (1978b) Pulmonary neuro-epithelial bodies. Ultrastucture, surface morphology and effects of pharmaca in vitro. In: Sturgess JM (ed) Electron microscopy. Toronto. pp 490–491
Cutz E, Chan W, Track NS (1981) Bombesin, calcitonin and leu-enkephalin immunoreactivity in endocrine cells of human lung. Experientia 37:765–767
Cutz E, Chan W, Kay JM, Chamberlain DW (1982) Immunoperoxidase staining for serotonin, bombesin, calcitonin, and leu-enkephalin in pulmonary tumorlets, bronchial carcinoids, and oat cell carcinomas. Lab Invest 46:16A
Cutz E, Gillan JE, Bryan AC (1985) Neuroendocrine cells in the developing human lung: morphologic and functional considerations. Pediatr Pulmonol 1:S21–S29
Cutz E, Speirs V, Yeger H, Newman C, Wang D, Perrin DG (1993) Cell biology of pulmonary neuroepithelial bodies-validation of an in vitro model.I. Effects of hypoxia and Ca2+ ionophore on serotonin content and exocytosis of dense cored vesicles. Anat Rec 236:41–52
Cutz E, Gillan JE, Perrin DG (1995) Pulmonary neuroendocrine cell system: an overview of cell biology and pathology with emphasis on pediatric lung disease. In: Askin FB, Langston HS, Rosenberg HS, Bernstein J (eds) Pulmonary disease. Karger, Basel, pp 23–70
Cutz E, Perrin DG, Hackman R, CzegledyNagy EN (1996) Maternal smoking and pulmonary neuroendocrine cells in sudden infant death syndrome. Pediatrics 98:668–672
Cutz E, Ma TK, Perrin DG, Moore AM, Becker LE (1997) Peripheral chemoreceptors in congenital central hypoventilation syndrome. Am J Respir Crit Care Med 155:358–363
Cutz E, Fu XW, Yeger H, Peers C, Kemp PJ (2003) Oxygen sensing in pulmonary neuroepithelial bodies and related tumor cell models. In: Lahiri S, Semenza GL, Prabhakar NR (eds) Lung oxygen sensing. Marcel Dekker, New York, pp 567–602
Cutz E, Fu XW, Yeger H (2004) Methods to study neuroepithelial bodies as airway oxygen sensors. Methods Enzymol 381:26–40
Cutz E, Perrin DG, Pan J, Haas EA, Krous HF (2007a) Pulmonary neuroendocrine cells and neuroepithelial bodies in sudden infant death syndrome: potential markers of airway chemoreceptor dysfunction. Pediatr Dev Pathol 10:106–116
Cutz E, Yeger H, Pan J (2007b) Pulmonary neuroendocrine cell system in pediatric lung disease—recent advances. Pediatr Dev Pathol 10:419–435
Cutz E, Fu XW, Yeger H, Pan J, Nurse CA (2009a) Oxygen sensing in mammalian pulmonary neuroepithelial bodies. In: Zaccone G, Cutz E, Adriaensen D, Nurse CA, Mauceri A (eds) Airway chemoreceptors in the vertebrates. Structure, evolution and function. Science Publishers, Enfield, New Hampshire, pp 269–290
Cutz E, Pan J, Yeger H (2009b) The role of NOX2 and ‘Novel oxidases’ in airway chemoreceptor O2 sensing. In: Gonzalez C, Nurse CA, Peers C (eds) Adv Exp Med Biol: arterial chemoreceptors. Springer, pp 427–438
Cutz E, Pan J, Yeger H, Domnik NJ, Fisher JT (2013) Recent advances and controversies on the role of pulmonary neuroepithelial bodies as airway sensors. Semin Cell Dev Biol 24:40–50
Dakhama A, Kanehiro A, Mäkelä MJ, Loader JE, Larsen GL, Gelfand EW (2002) Regulation of airway hyperresponsiveness by calcitonin gene-related peptide in allergen sensitised and challenged mice. Am J Respir Crit Care Med 165:1137–1144
Dakhama A, Larsen GL, Gelfand EW (2004) Calcitonin gene-related peptide: role in airway homeostasis. Curr Opin Pharmacol 4:215–220
De Proost I, Brouns I, Pintelon I, Timmermans J-P, Adriaensen D (2007a) Pulmonary expression of voltage-gated calcium channels: special reference to sensory airway receptors. Histochem Cell Biol 128:301–316
De Proost I, Pintelon I, Brouns I, Timmermans J-P, Adriaensen D (2007b) Selective visualisation of sensory receptors in the smooth muscle layer of ex vivo airway whole mounts by styryl pyridinium dyes. Cell Tissue Res 329:421–431
De Proost I, Pintelon I, Brouns I, Kroese ABA, Riccardi D, Kemp PJ, Timmermans J-P, Adriaensen D (2008) Functional live cell imaging of the pulmonary neuroepithelial body microenvironment. Am J Respir Cell Mol Biol 39(2):180–189
De Proost I, Pintelon I, Wilkinson WJ, Goethals S, Brouns I, Van Nassauw L, Riccardi D, Timmermans J-P, Kemp PJ, Adriaensen D (2009) Purinergic signaling in the pulmonary neuroepithelial body microenvironment unraveled by live cell imaging. FASEB J 23:1153–1160
De Spiegelaere W, Cornillie P, Van Poucke M, Peelman L, Burvenich C, Van den Broeck W (2011) Quantitative mRNA expression analysis in kidney glomeruli using microdissection techniques. Histol Histopathol 26:267–275
Delmotte P, Sanderson MJ (2006) Ciliary beat frequency is maintained at a maximal rate in the small airways of mouse lung slices. Am J Respir Cell Mol Biol 35:110–117
Deterding RR, Pye C, Fan LL, Langston C (2005) Persistent tachypnea of infancy is associated with neuroendocrine cell hyperplasia. Pediatr Pulmonol 40:157–165
Dey RD, Hoffpauir JM (1986) Ultrastructural colocalization of the bioactive mediators 5-hydroxytryptamine and bombesin in endocrine cells of human fetal airways. Cell Tissue Res 246:119–124
Dey RD, Altemus JB, Zervos I, Hoffpauir J (1990) Origin and colocalization of CGRP- and SP-reactive nerves in cat airway epithelium. J Appl Physiol 68:770–778
Ding J, Xiao Y, Lu D, Du YR, Cui XY, Chen J (2011) Effects of SKF-96365, a TRPC inhibitor, on melittin-induced inward current and intracellular Ca2+ rise in primary sensory cells. Neurosci Bull 27:135–142
Dinh QT, Groneberg DA, Mingomataj E, Peiser C, Heppt W, Dinh S, Arck PC, Klapp BF, Fischer A (2003) Expression of substance P and vanilloid receptor (VR1) in trigeminal sensory neurons projecting to the mouse nasal mucosa. Neuropeptides 37:245–250
Domnik NJ, Cutz E (2011) Pulmonary neuroepithelial bodies as airway sensors: putative role in the generation of dyspnea. Curr Opin Pharmacol 11(3):211–217
Domyan ET, Ferretti E, Throckmorton K, Mishina Y, Nicolis SK, Sun X (2011) Signaling through BMP receptors promotes respiratory identity in the foregut via repression of Sox2. Development 138:971–981
Donne ML, Lechner AJ, Rock JR (2015) Evidence for lung epithelial stem cell niches. BMC Dev Biol 15:32
Ebina M, Hoyt RF, McNelly NA, Sorokin SP, Linnoila RI (1997) Effects of hydrogen and bicarbonate ions on endocrine cells in fetal rat lung organ cultures. Am J Phsyiol 272:L178–L186
Eblaghie MC, Reedy M, Oliver T, Mishina Y, Hogan BL (2006) Evidence that autocrine signaling through Bmpr1a regulates the proliferation, survival and morphogenetic behavior of distal lung epithelial cells. Dev Biol 291:67–82
El Hiani Y, Ahidouch A, Lehen'kyi V, Hague F, Gouilleux F, Mentaverri R, Kamel S, Lassoued K, Brule G, Ouadid-Ahidouch H (2009) Extracellular signal-regulated kinases 1 and 2 and TRPC1 channels are required for calcium-sensing receptor-stimulated MCF-7 breast cancer cell proliferation. Cell Physiol Biochem 23:335–346
Emmert-Buck MR, Bonner RF, Smith PD, Chuaqui RF, Zhuang Z, Goldstein SR, Weiss RA, Liotta LA (1996) Laser capture microdissection. Science 274:998–1001
Feng G, Lu J, Gross J (2004) Generation of transgenic mice. Methods Mol Med 99:255–267
Fernandez-Fernandez D, Cadaveira-Mosquera A, Rueda-Ruzafa L, Herrera-Perez S, Veale EL, Reboreda A, Mathie A, Lamas JA (2018) Activation of TREK currents by riluzole in three subgroups of cultured mouse nodose ganglion neurons. PLoS One 13:e0199282
Feyrter F (1938) Uber diffuse endokrine epitheliale Organe. In: Barth JA (ed) Barth, Leipzig. pp 1–62
Feyrter F (1953) Über die peripheren endokrinen (parakrinen) Drüsen des Menschen. Wilhelm Maudrich, Wien
Fink M, Lesage F, Duprat F, Heurteaux C, Reyes R, Fosset M, Lazdunski M (1998) A neuronal two P domain K+ channel stimulated by arachidonic acid and polyunsaturated fatty acids. EMBO J 17:3297–3308
Finney BA, del Moral PM, Wilkinson WJ, Cayzac S, Cole M, Warburton D, Kemp PJ, Riccardi D (2008) Regulation of mouse lung development by the extracellular calcium-sensing receptor, CaR. J Physiol 586:6007–6019
Fleige S, Pfaffl MW (2006) RNA integrity and the effect on the real-time qRT-PCR performance. Mol Aspects Med 27:126–139
Freichel M, Zink-Lorenz A, Holloschi A, Hafner M, Flockerzi V, Raue F (1996) Expression of a calcium-sensing receptor in a human medullary thyroid carcinoma cell line and its contribution to calcitonin secretion. Endocrinology 137:3842–3848
Fröhlich F (1949) Die “Helle Zelle” der Bronchialschleimhaut und ihre Beziehungen zum Problem der Chemoreceptoren. Frankf Z Pathol 60:517–559
Fu XW, Spindel ER (2009) Recruitment of GABA(A) receptors in chemoreceptor pulmonary neuroepithelial bodies by prenatal nicotine exposure in monkey lung. Adv Exp Med Biol 648:439–445
Fu XW, Nurse CA, Wang YT, Cutz E (1999) Selective modulation of membrane currents by hypoxia in intact airway chemoreceptors from neonatal rabbit. J Physiol 514:139–150
Fu XW, Wang DS, Nurse CA, Dinauer MC, Cutz E (2000) NADPH oxidase is an O2 sensor in airway chemoreceptors: evidence from K+ current modulation in wild-type and oxidase-deficient mice. Proc Natl Acad Sci U S A 97:4374–4379
Fu XW, Wang D, Pan J, Farragher SM, Wong V, Cutz E (2001) Neuroepithelial bodies in mammalian lung express functional serotonin type 3 receptor. Am J Physiol Lung Cell Mol Physiol 281:L931–L940
Fu XW, Nurse CA, Wong V, Cutz E (2002) Hypoxia-induced secretion of serotonin from intact pulmonary neuroepithelial bodies in neonatal rabbit. J Physiol 539:503–510
Fu XW, Nurse CA, Farragher SM, Cutz E (2003) Expression of functional nicotinic acetylcholine receptors in neuroepithelial bodies of neonatal hamster lung. Am J Physiol Lung Cell Mol Physiol 285:1203–1212
Fu XW, Nurse C, Cutz E (2004) Expression of functional purinergic receptors in pulmonary neuroepithelial bodies and their role in hypoxia chemotransmission. Biol Chem 385:275–284
Fu XW, Nurse C, Cutz E (2007) Characterization of slowly inactivating KVα current in rabbit pulmonary neuroepithelial bodies: effects of hypoxia and nicotine. Am J Physiol Lung Cell Mol Physiol 293:L892–L902
Garg A, Sui P, Verheyden JM, Young LR, Sun X (2019) Consider the lung as a sensory organ: A tip from pulmonary neuroendocrine cells. Curr Top Dev Biol 132:67–89
Garrett JE, Tamir H, Kifor O, Simin RT, Rogers KV, Mithal A, Gagel RF, Brown EM (1995) Calcitonin-secreting cells of the thyroid express an extracellular calcium receptor gene. Endocrinology 136:5202–5211
George J, Lim JS, Jang SJ, Cun Y, Ozretic L, Kong G, Leenders F, Lu X, Fernandez-Cuesta L, Bosco G, Muller C, Dahmen I, Jahchan NS, Park KS, Yang D, Karnezis AN, Vaka D, Torres A, Wang MS, Korbel JO, Menon R, Chun SM, Kim D, Wilkerson M, Hayes N, Engelmann D, Putzer B, Bos M, Michels S, Vlasic I, Seidel D, Pinther B, Schaub P, Becker C, Altmuller J, Yokota J, Kohno T, Iwakawa R, Tsuta K, Noguchi M, Muley T, Hoffmann H, Schnabel PA, Petersen I, Chen Y, Soltermann A, Tischler V, Choi CM, Kim YH, Massion PP, Zou Y, Jovanovic D, Kontic M, Wright GM, Russell PA, Solomon B, Koch I, Lindner M, Muscarella LA, la Torre A, Field JK, Jakopovic M, Knezevic J, Castanos-Velez E, Roz L, Pastorino U, Brustugun OT, Lund-Iversen M, Thunnissen E, Kohler J, Schuler M, Botling J, Sandelin M, Sanchez-Cespedes M, Salvesen HB, Achter V, Lang U, Bogus M, Schneider PM, Zander T, Ansen S, Hallek M, Wolf J, Vingron M, Yatabe Y, Travis WD, Nurnberg P, Reinhardt C, Perner S, Heukamp L, Buttner R, Haas SA, Brambilla E, Peifer M, Sage J, Thomas RK (2015) Comprehensive genomic profiles of small cell lung cancer. Nature 524:47–53
Gerbino A, Colella M (2018) The different facets of extracellular calcium sensors: old and new concepts in calcium-sensing receptor signalling and pharmacology. Int J Mol Sci 19
Ghatei MA, Sheppard MN, Henzen-Logman S, Blank MA, Polak JM, Bloom SR (1983) Bombesin and vasoactive intestinal polypeptide in the developing lung: marked changes in acute respiratory distress syndrome. J Clin Endocrinol Metabolism 57:1226–1232
Giangreco A, Reynolds SD, Stripp BR (2002) Terminal bronchioles harbor a unique airway stem cell population that localizes to the bronchoalveolar duct junction. Am J Pathol 161:173–182
Gillan JE, Cutz E (1993) Abnormal bombesin immunoreactive cells in Wilson-Mikity syndrome (pulmonary dysmaturity) and bronchopulmonary dysplasia. Pediatr Pathol 13:165–180
Gillan JE, Curran C, O'Reilly E, Cahalane SF, Unwin AR (1989) Abnormal patterns of pulmonary neuroendocrine cells in victims of sudden infant death syndrome. Pediatrics 84:828–834
Giroux-Leprieur E, Costantini A, Ding VW, He B (2018) Hedgehog signaling in lung cancer: from oncogenesis to cancer treatment resistance. Int J Mol Sci 19:2835
Glaser T, Cappellari AR, Pillat MM, Iser IC, Wink MR, Battastini AM, Ulrich H (2012) Perspectives of purinergic signaling in stem cell differentiation and tissue regeneration. Purinergic Signal 8:523–537
Glazebrook PA, Schilling WP, Kunze DL (2005) TRPC channels as signal transducers. Pflugers Arch- Eur J Physiol 451:125–130
Gomes RN, Castro-Faria-Neto HC, Bozza PT, Soares MB, Shoemaker CB, David JR, Bozza MT (2005) Calcitonin gene-related peptide inhibits local acute inflammation and protects mice against lethal endotoxemia. Shock 24:590–594
Gomis A, Soriano S, Belmonte C, Viana F (2008) Hypoosmotic- and pressure-induced membrane stretch activate TRPC5 channels. J Physiol 586:5633–5649
Gosney J, Heath D, Smith P, Harris P, Yacoub M (1989a) Pulmonary endocrine cells in pulmonary arterial disease. Arch Pathol Lab Med 113:337–341
Gosney JR (1992) Pulmonary endocrine pathology. Endocrine cells and endocrine tumours of the lung. Butterworth-Heinemann, Oxford
Gosney JR (1993) Neuroendocrine cell populations in postnatal human lungs: minimal variation from childhood to old age. Anat Rec 263:177–180
Gosney JR (1997) Pulmonary neuroendocrine cell system in pediatric and adult lung disease. Microsc Res Tech 37:107–113
Gosney JR, Sissons M, Allibone RO, Blakey AF (1989b) Pulmonary endocrine cells in chronic bronchitis and emphysema. J Pathol 157:127–133
Gould VE, Linnoila RI, Memoli VA, Warren WH (1983) Neuroendocrine components of the bronchopulmonary tract: hyperplasia, dysplasias and neoplasms. Lab Invest 49:519–537
Gray E, Muller D, Squires PE, Asare-Anane H, Huang GC, Amiel S, Persaud SJ, Jones PM (2006) Activation of the extracellular calcium-sensing receptor initiates insulin secretion from human islets of Langerhans: involvement of protein kinases. J Endocrinol 190:703–710
Gu X, Karp PH, Brody SL, Pierce RA, Welsh MJ, Holtzman MJ, Ben-Shahar Y (2014) Chemosensory functions for pulmonary neuroendocrine cells. Am J Respir Cell Mol Biol 50:637–646
Guha A, Vasconcelos M, Cai Y, Yoneda M, Hinds A, Qian J, Li G, Dickel L, Johnson JE, Kimura S, Guo J, McMahon J, McMahon AP, Cardoso WV (2012) Neuroepithelial body microenvironment is a niche for a distinct subset of Clara-like precursors in the developing airways. Proc Natl Acad Sci U S A 109:12592–12597
Guha A, Vasconcelos M, Zhao R, Gower AC, Rajagopal J, Cardoso WV (2014) Analysis of Notch signaling-dependent gene expression in developing airways reveals diversity of Clara cells. PLoS One 9
Guha A, Deshpande A, Jain A, Sebastiani P, Cardoso WV (2017) Uroplakin 3a(+) cells are a distinctive population of epithelial progenitors that contribute to airway maintenance and post-injury repair. Cell Rep 19:246–254
Gupta RP, Patton SE, Jetten AM, Hook GE (1987) Purification, characterization and proteinase-inhibitory activity of a Clara-cell secretory protein from the pulmonary extracellular lining of rabbits. Biochem J 248:337–344
Haeberle H, Bryan LA, Vadakkan TJ, Dickinson ME, Lumpkin EA (2008) Swelling-activated Ca2+ channels trigger Ca2+ signals in Merkel cells. PLoS One 3:e1750
Haller CJ (1994) The ontogeny and function of neuroepithelial bodies in the lung of the mouse and the rat. Masters of Science thesis, University of Queensland, Brisbane, Australia
Hamilton G, Rath B (2015) Smoking, inflammation and small cell lung cancer: recent developments. Wien Med Wochenschr 165:379–386
Hannan FM, Babinsky VN, Thakker RV (2016) Disorders of the calcium-sensing receptor and partner proteins: insights into the molecular basis of calcium homeostasis. J Mol Endocrinol 57:R127–R142
Harris KS, Zhang Z, McManus MT, Harfe BD, Sun X (2006) Dicer function is essential for lung epithelium morphogenesis. Proc Natl Acad Sci U S A 103:2208–2213
Harteneck C, Reiter B (2007) TRP channels activated by extracellular hypo-osmoticity in epithelia. Biochem Soc Trans 35:91–95
Hartness ME, Lewis A, Searle GJ, O'Kelly I, Peers C, Kemp PJ (2001) Combined antisense and pharmacological approaches implicate hTASK as an airway O2 sensing K+ channel. J Biol Chem 276:26499–26508
Heath D, Yacoub M, Gosney JR, Madden B, Caslin AW, Smith P (1990) Pulmonary endocrine cells in hypertensive pulmonary vascular disease. Histopathology 16:21–28
Helset E, Kjaeve J, Bjertnaes L, Lundberg JM (1995) Acute alveolar hypoxia increases endothelin-1 release but decreases release of calcitonin gene-related peptide in isolated perfused rat lungs. Scand J Clin Lab Invest 55:369–376
Hennel M, Harsanyiova J, Ru F, Zatko T, Brozmanova M, Trancikova A, Tatar M, Kollarik M (2018) Structure of vagal afferent nerve terminal fibers in the mouse trachea. Respir Physiol Neurobiol 249:35–46
Hering E (1868) Die Selbesteuerung der Athmung durch den Nervus vagus. Sber Akad Wiss Wein 57:672–677
Hogan BL, Barkauskas CE, Chapman HA, Epstein JA, Jain R, Hsia CC, Niklason L, Calle E, Le A, Randell SH, Rock J, Snitow M, Krummel M, Stripp BR, Vu T, White ES, Whitsett JA, Morrisey EE (2014) Repair and regeneration of the respiratory system: complexity, plasticity, and mechanisms of lung stem cell function. Cell stem cell 15:123–138
Hong KU, Reynolds SD, Giangreco A, Hurley CM, Stripp BR (2001) Clara cell secretory protein-expressing cells of the airway neuroepithelial body microenvironment include a label-retaining subset and are critical for epithelial renewal after progenitor cell depletion. Am J Respir Cell Mol Biol 24:671–681
Hor P, Punj V, Calvert BA, Castaldi A, Miller AJ, Carraro G, Stripp BR, Brody SL, Spence JR, Ichida JK, Ryan Firth AL, Borok Z (2020). Efficient generation and transcriptomic profiling of human iPSC-Derived pulmonary neuroendocrine cells. iScience 23:101083
Housley GD, Bringmann A, Reichenbach A (2009) Purinergic signaling in special senses. Trends Neurosci 32:128–141
Hoyt RF Jr, McNelly NA, Sorokin SP (1990) Dynamics of neuroepithelial body (NEB) formation in developing hamster lung: light microscopic autoradiography after 3H-thymidine labeling in vivo. Anat Rec 227:340–350
Hoyt RF, Feldman H, Sorokin SP (1982) Neuroepithelial bodies (NEB) and solitary endocrine cells in the hamster lung. Exp Lung Res 3:299–311
Hsu CC, Ruan T, Lee LY, Lin YS (2019) Stimulatory effect of 5-Hydroxytryptamine (5-HT) on rat capsaicin-sensitive lung vagal sensory neurons via activation of 5-HT3 receptors. Front Physiol 10:642
Hung K-S (1982) Development of neuroepithelial bodies in pre- and postnatal mouse lungs: scanning electron microscopic study. Anat Rec 203:285–291
Hung K-S, Loosli CG (1974) Bronchiolar neuro-epithelial bodies in the neonatal mouse lungs. Am J Anat 140:191–200
Hung K-S, Hertweck MS, Hardy JD, Loosli CG (1973) Ultrastructure of nerves and associated cells in bronchiolar epithelium of the mouse lung. J Ultrastr Res 43:426–437
Hung K-S, Chapman AL, Mestemacher MA (1979) Scanning electron microscopy of bronchiolar neuroepithelial bodies in neonatal mouse lungs. Anat Rec 193:913–926
Ijsselstijn H, Gaillard JL, de Jongste JC, Tibboel D, Cutz E (1997) Abnormal expression of pulmonary bombesin-like peptide immunostaining cells in infants with congenital diaphragmatic hernia. Pediatr Res 42:715–720
Ito T, Udaka N, Yazawa T, Okudela K, Hayashi H, Sudo T, Guillemot F, Kageyama R, Kitamura H (2000) Basic helix-loop-helix transcription factors regulate the neuroendocrine differentiation of fetal mouse pulmonary epithelium. Development 127:3913–3921
Ito T, Udaka N, Ikeda M, Yazawa T, Kageyama R, Kitamura H (2001) Significance of proneural basic helix-loop-helix transcription in neuroendocrine differentiation of fetal lung epithelial cells and lung carcinoma. Histol Histopathol 16:335–343
Ito T, Ogura T, Ogawa N, Udaka N, Hayashi H, Inayama Y, Yazawa T, Kitamura H (2002) Modulation of pulmonary neuroendocrine cells in idiopathic interstitial pneumonia. Histol Histopathol 17:1121–1127
Ito T, Kudoh S, Ichimura T, Fujino K, Hassan WA, Udaka N (2017) Small cell lung cancer, an epithelial to mesenchymal transition (EMT)-like cancer: significance of inactive Notch signaling and expression of achaete-scute complex homologue 1. Hum Cell 30:1–10
Jammes Y, Fornaris E, Mei N, Barrat E (1982) Afferent and efferent components of the bronchial vagal branches in the cat. J Auton Nerv Syst 5:165–176
Jensen RT, Battey JF, Spindel ER, Benya RV (2008) International Union of Pharmacology. LXVIII. Mammalian bombesin receptors: nomenclature, distribution, pharmacology, signaling, and functions in normal and disease states. Pharmacol Rev 60:1–42
Jiramethee N, Erasmus D, Nogee L, Khoor A (2017) Pulmonary neuroendocrine cell hyperplasia associated with surfactant protein C gene mutation. Case Rep Pulmonol 2017:9541419
Johnson DE, Wobken JD (1987) Calcitonin gene-related peptide immunoreactivity in airway epithelial cells of the human fetus and infant. Cell Tissue Res 250:579–583
Johnson DE, Lock JE, Elde RP, Thompson TR (1982) Pulmonary neuroendocrine cells in hyaline membrane disease and bronchopulmonary dysplasia. Pediatr Res 16:446–454
Johnson DE, Kulik TJ, Lock JE, Elde RP, Thompson TR (1985) Bombesin-, calcitonin-, and serotonin-immunoreactive pulmonary neuroendocrine cells in acute and chronic neonatal lung disease. Pediatr Pulmonol 1(Suppl 3):S13–S20
Johnson DE, Wobken JD, Landrum BG (1988) Changes in the number of pulmonary neuroendocrine cells immunoreactive for bombesin, calcitonin, and serotonin in cystic fibrosis and following prolonged mechanic ventilation. Ann NY Acad Sci 547:534–535
Johnson DE, Anderson WR, Burke BA (1993) Pulmonary neuroendocrine cells in pediatric lung disease: alterations in airway structure in infants with bronchopulmonary dysplasia. Anat Rec 236:115–119
Jull BA, Plummer III HK, Schuller HM (2001) Nicotinic receptor-mediated activation by the tobacco-specific nitrosamine NNK of a Raf-1/MAP kinase pathway,resulting in phosphorylation of c-myc in human small cell lung carcinoma cells and pulmonary neuroendocrine cells. J Cancer Res Oncol 127:707–717
Jung H, Yoon BC, Holt CE (2012) Axonal mRNA localization and local protein synthesis in nervous system assembly, maintenance and repair. Nat Rev Neurosci 13:308–324
Kaczynska K, Szereda-Przestaszewska M (2009) Peripheral cardiorespiratory effects of bombesin in anaesthetized rats. Eur J Pharmacol 602:157–162
Kasacka I, Azzadin A, Sawicki B, Malla H (2001) Immunoreactivity of neuroendocrine cells in the respiratory tract in rats with experimental uremia after thyroparathyroidectomy. Folia Histochem Cytobiol 39(Suppl 2):64–65
Kauffman SL (1980) Cell proliferation in the mammalian lung. Int Rev Exp Pathol 22:131–191
Keith IM, Pelto-Huikko M, Schalling M, Hokfelt T (1991) Calcitonin gene-related peptide and its mRNA in pulmonary neuroendocrine cells and ganglia. Histochemistry 96:311–315
Kemp PJ, Peers C (2009) Enzyme-linked acute oxygen sensing in airway and arterial chemoreceptors—invited article. Adv Exp Med Biol 648:39–48
Kemp PJ, Searle GJ, Hartness ME, Lewis A, Miller P, Williams S, Wootton P, Adriaensen D, Peers C (2003) Acute oxygen sensing in cellular models: relevance to the physiology of pulmonary neuroepithelial and carotid bodies. Anat Rec A Discov Mol Cell Evol Biol 270:41–50
Kerman IA, Buck BJ, Evans SJ, Akil H, Watson SJ (2006) Combining laser capture microdissection with quantitative real-time PCR: effects of tissue manipulation on RNA quality and gene expression. J Neurosci Methods 153:71–85
Kiefer JC (2011) Primer and interviews: the dynamic stem cell niche. Dev Dyn 240:737–743
Kim D (2003) Fatty acid-sensitive two-pore domain K+ channels. Trends Pharmacol Sci 24:648–654
Kim D (2005) Physiology and pharmacology of two-pore domain potassium channels. Curr Pharm Des 11:2717–2736
Kim H, Kim M, Im SK, Fang S (2018) Mouse Cre-LoxP system: general principles to determine tissue-specific roles of target genes. Lab Anim Res 34:147–159
Kinnamon SC, Finger TE (2013) A taste for ATP: neurotransmission in taste buds. Front Cell Neurosci 7:264
Kiyokawa H, Morimoto M (2020) Notch signaling in the mammalian respiratory system, specifically the trachea and lungs, in development, homeostasis, regeneration, and disease. Dev Growth Differ 62:67–79
Klug J, Beier HM, Bernard A, Chilton BS, Fleming TP, Lehrer RI, Miele L, Pattabiraman N, Singh G (2000) Uteroglobin/Clara cell 10-kDa family of proteins: nomenclature committee report. Ann N Y Acad Sci 923:348–354
Koliakos E, Thomopoulos T, Abbassi Z, Duc C, Christodoulou M (2017) Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: a case report and review of the literature. Am J Case Rep 18:975–979
Kratz JR, Yagui-Beltran A, Jablons DM (2010) Cancer stem cells in lung tumorigenesis. Ann Thorac Surg 89:S2090–S2095
Kubin L, Alheid GF, Zuperku EJ, McCrimmon DR (2006) Central pathways of pulmonary and lower airway vagal afferents. J Appl Physiol 101:618–627
Kummer W, Fischer A, Kurkowski R, Heym C (1992) The sensory and sympathetic innervation of guinea-pig lung and trachea as studied by retrograde neuronal tracing and double-labelling immunohistochemistry. Neuroscience 49:715–737
Kuo CS, Krasnow MA (2015) Formation of a neurosensory organ by epithelial cell slithering. Cell 163:394–405
Lamb JP, Sparrow MP (2002) Three-dimensional mapping of sensory innervation with substance P in porcine bronchial mucosa: comparison with human airways. Am J Respir Crit Care Med 166:1269–1281
Lauweryns JM, Cokelaere M (1973) Hypoxia-sensitive neuro-epithelial bodies. Intrapulmonary secretory neuroreceptors modulated by the CNS. Z Zellforsch:521–540
Lauweryns JM, Peuskens JC (1972) Neuro-epithelial bodies (neuroreceptor or secretory organs?) in human infant bronchial and bronchiolar epithelium. Anat Rec 172:471–481
Lauweryns JM, Van Lommel A (1982) Morphometric analysis of hypoxia-induced synaptic activity in intrapulmonary neuroepithelial bodies. Cell Tissue Res 226:201–214
Lauweryns JM, Van Ranst L (1987) Calcitonin gene related peptide immunoreactivity in rat lung: light and electron microscopic study. Thorax 42:183–189
Lauweryns JM, Cokelaere M, Theunynck P (1972) Neuroepithelial bodies in the respiratory mucosa of various mammals. A light optical, histochemical and ultrastuctural investigation. Z Zellforsch Mikrosk Anat 135:569–592
Lauweryns JM, Cokelaere M, Theunynck P (1973) Serotonin producing neuroepithelial bodies in rabbit respiratory mucosa. Science 180:410–413
Lauweryns JM, Cokelaere M, Deleersnyder M, Liebens M (1977) Intrapulmonary neuro-epithelial bodies in newborn rabbits. Influence of hypoxia, hyperoxia, hypercapnia, nicotine, reserpine, L-DOPA and 5-HTP. Cell Tissue Res 182:425–440
Lauweryns JM, Cokelaere M, Lerut T, Theunynck P (1978) Cross-circulation studies on the influence of hypoxia and hypoxaemia on neuro-epithelial bodies in young rabbits. Cell Tissue Res 193:373–386
Lauweryns JM, de Bock V, Verhofstad AA, Steinbusch HW (1982) Immunohistochemical localization of serotonin in intrapulmonary neuro-epithelial bodies. Cell Tissue Res 226:215–223
Lauweryns JM, Tierens A, Decramer M (1990) Influence of hypercapnia on rabbit intra-pulmonary neuroepithelial bodies: microfluorimetric and morphometric study. Eur Respir J 3:182–186
Leach JP, Morrisey EE (2018) Repairing the lungs one breath at a time: how dedicated or facultative are you? Genes Dev 32:1461–1471
Lee L-Y, Pisarri TE (2001) Afferent properties and reflex functions of bronchopulmonary C-fibers. Respir Physiol 125:47–65
Lee L-Y, Undem BJ (2005) Bronchopulmonary vagal afferent nerves. In: Undem BJ, Weinreich D (eds) “Advances in vagal afferent neurobiology”, frontiers in neuroscience series, 1st edn. CRC Press, Boca Raton, pp 279–313
Lee L-Y, Yu J (2014) Sensory nerves in lung and airways. Compr Physiol 4:287–324
Lee L-Y, Lin YS, Gu Q, Chung E, Ho CY (2003) Functional morphology and physiological properties of bronchopulmonary C-fiber afferents. Anat Rec 270(A):17–24
Lee SH, Iwanaga T, Fujita T (1995) Intraepithelial nerve fibers in the nasal mucosa of the rat with special reference to the localization of CGRP, VIP and nitric oxide (NO). Arch Histol Cytol 58:449–456
Lembrechts R, Pintelon I, Schnorbusch K, Timmermans J-P, Adriaensen D, Brouns I (2011) Expression of mechanogated two-pore-domain potassium channels in mouse lungs: special reference to mechanosensory airway receptors. Histochem Cell Biol 136:371–385
Lembrechts R, Brouns I, Schnorbusch K, Pintelon I, Timmermans JP, Adriaensen D (2012) Neuroepithelial bodies as mechanotransducers in the intrapulmonary airway epithelium: involvement of TRPC5. Am J Respir Cell Mol Biol 47:315–323
Lembrechts R, Brouns I, Schnorbusch K, Pintelon I, Kemp PJ, Timmermans JP, Riccardi D, Adriaensen D (2013) Functional expression of the multimodal extracellular calcium-sensing receptor in pulmonary neuroendocrine cells. J Cell Sci 126:4490–4501
Leonetti A, Facchinetti F, Minari R, Cortellini A, Rolfo CD, Giovannetti E, Tiseo M (2019) Notch pathway in small-cell lung cancer: from preclinical evidence to therapeutic challenges. Cell Oncol (Dordr) 42:261–273
Lesage F, Lazdunski M (2000) Molecular and functional properties of two-pore-domain potassium channels. Am J Physiol Renal Physiol 279:F793–F801
Lewis A, Hartness ME, Chapman CG, Fearon IM, Meadows HJ, Peers C, Kemp PJ (2001) Recombinant hTASK1 is an O2-sensitive K+ channel. Biochem Biophys Res Commun 285:1290–1294
Lewis A, Miller P, Searle GJ, Hartness ME, Peers C, Kemp PJ (2002) Oxygen sensing by two members of the human tandem P domain K+ channel family (K2P), hTASK3 and hTREK1. FASEB J 16:A61
Lewis J (1998) Notch signalling. A short cut to the nucleus. Nature 393:304–305
Li F, He J, Wei J, Cho WC, Liu X (2015) Diversity of epithelial stem cell types in adult lung. Stem cells international 2015:728307
Li K, Nagalla SR, Spindel ER (1994) A rhesus monkey model to characterize the role of gastrin-releasing peptide (GRP) in lung development. Evidence for stimulation of airway growth. J Clin Invest 94:1605–1615
Li Y, Linnoila RI (2012) Multidirectional differentiation of Achaete-Scute homologue-1-defined progenitors in lung development and injury repair. Am J Respir Cell Mol Biol 47:768–775
Liberati TA, Randle MR, Toth LA (2010) In vitro lung slices: a powerful approach for assessment of lung pathophysiology. Expert Rev Mol Diagn 10:501–508
Lim JS, Ibaseta A, Fischer MM, Cancilla B, O’Young G, Cristea S, Luca VC, Yang D, Jahchan NS, Hamard C, Antoine M, Wislez M, Kong C, Cain J, Liu YW, Kapoun AM, Garcia KC, Hoey T, Murriel CL, Sage J (2017) Intratumoural heterogeneity generated by Notch signalling promotes small-cell lung cancer. Nature 545:360–364
Linnoila RI (2006) Functional facets of the pulmonary neuroendocrine system. Lab Invest 86:425–444
Linnoila RI, Zhao B, DeMayo JL, Nelkin BD, Baylin SB, DeMayo FJ, Ball DW (2000) Constitutive achaete-scute homologue-1 promotes airway dysplasia and lung neuroendocrine tumors in transgenic mice. Cancer Res 60:4005–4009
Liu G, Betts C, Cunoosamy DM, Aberg PM, Hornberg JJ, Sivars KB, Cohen TS (2019) Use of precision cut lung slices as a translational model for the study of lung biology. Respir Res 20:162
Liu T, Yang L, Han X, Ding X, Li J, Yang J (2020) Local sympathetic innervations modulate the lung innate immune responses. Sci Adv 6:eaay1497
Liu X, Driskell RR, Engelhardt JF (2006) Stem cells in the lung. Methods Enzymol 419:285–321
Livermore S, Zhou Y, Pan J, Yeger H, Nurse CA, Cutz E (2015) Pulmonary neuroepithelial bodies are polymodal airway sensors: evidence for CO2/H+ sensing. Am J Physiol Lung Cell Mol Physiol 308:L807–L815
Lo CCW, Moosavi SM, Bubb KJ (2018) The regulation of pulmonary vascular tone by neuropeptides and the implications for pulmonary hypertension. Front Physiol 9:1167
López-Barneo J (1994) Oxygen-sensitive ion channels: how ubiquitous are they? Trends Neurosci 17:133–135
Lorenzo IM, Liedtke W, Sanderson MJ, Valverde MA (2008) TRPV4 channel participates in receptor-operated calcium entry and ciliary beat frequency regulation in mouse airway epithelial cells. Proc Natl Acad Sci USA 105:12611–12616
Lundin A, Driscoll B (2013) Lung cancer stem cells: progress and prospects. Cancer Lett 338:89–93
Luts A, Uddman R, Absood A, Håkanson R, Sundler F (1991) Chemical coding of endocrine cells of the airways: presence of helodermin-like peptides. Cell Tissue Res 265:425–433
Luts A, Uddman R, Hakanson R, Sundler F (1994) Calcitonin, CGRP and helodermin in endocrine cells of the developing rat lung. Regul Pept 51:121–129
Lynch TJ, Engelhardt JF (2014) Progenitor cells in proximal airway epithelial development and regeneration. J Cell Biochem 115:1637–1645
Maingret F, Fosset M, Lesage F, Lazdunski M, Honore E (1999) TRAAK is a mammalian neuronal mechano-gated K+ channel. J Biol Chem 274:1381–1387
Marchevsky AM, Walts AE (2015) Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH). Semin Diagn Pathol 32:438–444
Martinac B (2004) Mechanosensitive ion channels: molecules of mechanotransduction. J Cell Sci 117:2449–2460
Martling C-R, Saria A, Fischer JA, Hökfelt T, Lundberg JM (1988) Calcitonin gene-related peptide and the lung: neuronal coexistence with substance P, release by capsaicin and vasodilatory effect. Regul Pept 20:125–139
Matute-Bello G, Frevert CW, Martin TR (2008) Animal models of acute lung injury. Am J Physiol Lung Cell Mol Physiol 295:L379–L399
Mazzone SB (2005) An overview of the sensory receptors regulating cough. Cough 1:2
Mazzone SB, Undem BJ (2016) Vagal afferent innervation of the Airways in Health and Disease. Physiol Rev 96:975–1024
McBride JT, Springall DR, Winter RJ, Polak JM (1990) Quantitative immunocytochemistry shows calcitonin gene-related peptide-like immunoreactivity in lung neuroendocrine cells is increased by chronic hypoxia in the rat. Am J Respir Cell Mol Biol 3:587–593
Medeiros F, Rigl CT, Anderson GG, Becker SH, Halling KC (2007) Tissue handling for genome-wide expression analysis: a review of the issues, evidence, and opportunities. Arch Pathol Lab Med 131:1805–1816
Meuwissen R, Berns A (2005) Mouse models for human lung cancer. Genes Dev 19:643–664
Miyazono K, Maeda S, Imamura T (2005) BMP receptor signaling: transcriptional targets, regulation of signals, and signaling cross-talk. Cytokine Growth Factor Rev 16:251–263
Miyazono K, Kamiya Y, Morikawa M (2010) Bone morphogenetic protein receptors and signal transduction. J Biochem 147:35–51
Montuenga LM, Guembe L, Burrell MA, Bodegas ME, Calvo A, Sola JJ, Sesma P, Villaro CA (2003) The diffuse endocrine system: from embryogenesis to carcinogenesis. Prog Histochem Cytochem 38:155–272
Moody TW, Ramos-Alvarez I, Jensen RT (2018) Neuropeptide G protein-coupled receptors as oncotargets. Front Endocrinol (Lausanne) 9:345
Morimoto M, Nishinakamura R, Saga Y, Kopan R (2012) Different assemblies of Notch receptors coordinate the distribution of the major bronchial Clara, ciliated and neuroendocrine cells. Development 139:4365–4373
Nabhan AN, Brownfield DG, Harbury PB, Krasnow MA, Desai TJ (2018) Single-cell Wnt signaling niches maintain stemness of alveolar type 2 cells. Science 359:1118–1123
Naizhen X, Kido T, Yokoyama S, Linnoila RI, Kimura S (2019) Spatiotemporal expression of three secretoglobin proteins, SCGB1A1, SCGB3A1, and SCGB3A2, in Mouse Airway Epithelia. J Histochem Cytochem 67:453–463
Neuhaus V, Danov O, Konzok S, Obernolte H, Dehmel S, Braubach P, Jonigk D, Fieguth HG, Zardo P, Warnecke G, Martin C, Braun A, Sewald K (2018) Assessment of the cytotoxic and immunomodulatory effects of substances in human precision-cut lung slices. J Vis Exp 135:57042
Noguchi M, Sumiyama K, Morimoto M (2015) Directed migration of pulmonary neuroendocrine cells toward airway branches organizes the stereotypic location of neuroepithelial bodies. Cell Rep 13:2679–2686
Nonomura K, Woo SH, Chang RB, Gillich A, Qiu Z, Francisco AG, Ranade SS, Liberles SD, Patapoutian A (2017) Piezo2 senses airway stretch and mediates lung inflation-induced apnoea. Nature 541:176–181
Oh EJ, Mazzone SB, Canning BJ, Weinreich D (2006) Reflex regulation of airway sympathetic nerves in guinea-pigs. J Physiol 573:549–564
Okada T, Shimizu S, Wakamori M, Maeda A, Kurosaki T, Takada N, Imoto K, Mori Y (1998) Molecular cloning and functional characterization of a novel receptor-activated TRP Ca2+ channel from mouse brain. J Biol Chem 273:10279–10287
O’Kelly I, Peers C, Kemp PJ (1998) O2-sensitive K+ channels in neuroepithelial body-derived small cell carcinoma cells of the human lung. Am J Physiol 275:L709–L716
O’Kelly I, Lewis A, Peers C, Kemp PJ (2000) O2 sensing by airway chemoreceptor-derived cells: protein kinase C activation reveals functional evidence for involvement of NADPH oxidase. J Biol Chem 275:7684–7692
Oswald RE, Suchyna TM, McFeeters R, Gottlieb P, Sachs F (2002) Solution structure of peptide toxins that block mechanosensitive ion channels. J Biol Chem 277:34443–34450
Ouadah Y, Rojas ER, Riordan DP, Capostagno S, Kuo CS, Krasnow MA (2019) Rare pulmonary neuroendocrine cells are stem cells regulated by Rb, p53, and notch. Cell 179(403–416):e423
Oztay F, Brouns I, Pintelon I, Raab M, Neuhuber W, Timmermans JP, Adriaensen D (2010) Neurotrophin-4 dependency of intraepithelial vagal sensory nerve terminals that selectively contact pulmonary NEBs in mice. Histol Histopathol 25:975–984
Pack RJ, Barker S, Howe A (1986) The effect of hypoxia on the number of amine-containing cells in the lung of the adult rat. Eur J Respir Dis 68:121–130
Pan J, Yeger H, Cutz E (2004) Innervation of pulmonary neuroendocrine cells and neuroepithelial bodies in developing rabbit lung. J Histochem Cytochem 52:379–389
Pan J, Copland I, Post M, Yeger H, Cutz E (2006) Mechanical stretch-induced serotonin release from pulmonary neuroendocrine cells: implications for lung development. Am J Physiol Lung Cell Mol Physiol 290:L185–L193
Park KS, Liang MC, Raiser DM, Zamponi R, Roach RR, Curtis SJ, Walton Z, Schaffer BE, Roake CM, Zmoos AF, Kriegel C, Wong KK, Sage J, Kim CF (2011) Characterization of the cell of origin for small cell lung cancer. Cell Cycle 10:2806–2815
Patel AJ, Honore E (2001) Properties and modulation of mammalian 2P domain K+ channels. Trends Neurosci 24:339–346
Peake JL, Reynolds SD, Stripp BR, Stephens KE, Pinkerton KE (2000) Alteration of pulmonary neuroendocrine cells during epithelial repair of naphthalene-induced airway injury. Am J Pathol 156:279–286
Pearsall AD, Hoyt RF, Sorokin SP (1985) Three-dimensional reconstruction of a small-granule paracrine cell cluster in an adult hamster bronchus. Anat Rec 212:132–142
Peers C, Kemp PJ (2001) Acute oxygen sensing: diverse but convergent mechanisms in airway and arterial chemoreceptors. Respir Res 2:145–149
Peng T, Frank DB, Kadzik RS, Morley MP, Rathi KS, Wang T, Zhou S, Cheng L, Lu MM, Morrisey EE (2015) Hedgehog actively maintains adult lung quiescence and regulates repair and regeneration. Nature 526:578–582
Perez JF, Sanderson MJ (2005) The frequency of calcium oscillations induced by 5-HT, Ach, and KCl determine the contraction of smooth muscle cells of intrapulmonary bronchioles. J Gen Physiol 125:535–553
Perez-Novo CA, Claeys C, Speleman F, Van Cauwenberge P, Bachert C, Vandesompele J (2005) Impact of RNA quality on reference gene expression stability. BioTechniq 39:52,54,56
Perrin DG, McDonald TJ, Cutz E (1991) Hyperplasia of bombesin-immunoreactive pulmonary neuroendocrine cells and neuroepithelial bodies in sudden infant death syndrome. Pediatr Pathol 11:431–447
Pintelon I, De Proost I, Brouns I, Van Herck H, Van Genechten J, Van Meir F, Timmermans J-P, Adriaensen D (2005) Selective visualisation of neuroepithelial bodies in vibratome slices of living lung by 4-Di-2-ASP in various animal species. Cell Tissue Res 321:21–33
Piskuric NA, Nurse CA (2013) Expanding role of ATP as a versatile messenger at carotid and aortic body chemoreceptors. J Physiol 591:415–422
Plopper CG, Macklin J, Nishio SJ, Hyde DM, Buckpitt AR (1992a) Relationship of Cytochrome-P-450 activity to Clara cell cytotoxicity.3. Morphometric comparison of changes in the epithelial populations of terminal bronchioles and Lobar Bronchi in mice, hamsters, and rats after parenteral administration of naphthalene. Lab Invest 67:553–556
Plopper CG, Suverkropp C, Morin D, Nishio S, Buckpitt A (1992b) Relationship of Cytochrome-P-450 activity to clara cell cytotoxicity.1. Histopathologic comparison of the respiratory-tract of mice, rats and hamsters after parenteral administration of naphthalene. J Pharmacol Exp Therap 261:353–363
Plummer HK 3rd, Dhar M, Schuller HM (2005) Expression of the alpha7 nicotinic acetylcholine receptor in human lung cells. Respir Res 6:29
Plummer HKI, Sheppard B, Schuller HM (2000) Interaction of tobacco-specific toxicants with nicotinic cholinergic regulation of pulmonary neuroendocrine cells: implications for pediatric lung disease. Exp Lung Res 26:121–135
Polak JM, Becker KL, Cutz E, Gail DB, Goniakowska-Witalinska L, Gosney JR, Lauweryns JM, Linnoila I, McDowell EM, Miller YE (1993) Lung endocrine cell markers, peptides, and amines. Anat Rec 236:169–171
Popler J, Gower WA, Mogayzel PJ Jr, Nogee LM, Langston C, Wilson AC, Hay TC, Deterding RR (2010) Familial neuroendocrine cell hyperplasia of infancy. Pediatr Pulmonol 45:749–755
Porzionato A, Macchi V, Parenti A, Matturri L, De CR (2008) Peripheral chemoreceptors: postnatal development and cytochemical findings in sudden infant death syndrome. Histol Histopathol 23:351–365
Potenzieri C, Meeker S, Undem BJ (2012) Activation of mouse bronchopulmonary C-fibres by serotonin and allergen-ovalbumin challenge. J Physiol 590:5449–5459
Pushpalatha KV, Besse F (2019) Local translation in axons: when membraneless RNP granules meet membrane-bound organelles. Front Mol Biosci 6:129
Qing X, Svaren J, Keith IM (2001) mRNA expression of novel CGRP1 receptors and their activity-modifying proteins in hypoxic rat lung. Am J Physiol Lung Cell Mol Physiol 280:L547–L554
Ramos-Alvarez I, Moreno P, Mantey SA, Nakamura T, Nuche-Berenguer B, Moody TW, Coy DH, Jensen RT (2015) Insights into bombesin receptors and ligands: Highlighting recent advances. Peptides 72:128–144
Rapp J, Jaromi L, Kvell K, Miskei G, Pongracz JE (2017) WNT signaling—lung cancer is no exception. Respir Res 18:167
Rawlins EL (2015) Stem cells: emergency back-up for lung repair. Nature 517:556–557
Rawlins EL, Okubo T, Que J, Xue Y, Clark C, Luo X, Hogan BL (2008) Epithelial stem/progenitor cells in lung postnatal growth, maintenance, and repair. Cold Spring Harb Symp Quant Biol 73:291–295
Rawlins EL, Okubo T, Xue Y, Brass DM, Auten RL, Hasegawa H, Wang F, Hogan BL (2009) The role of Scgb1a1+ Clara cells in the long-term maintenance and repair of lung airway, but not alveolar, epithelium. Cell Stem Cell 4:525–534
Reguart N, Marin E, Remon J, Reyes R, Teixido C (2020) In search of the long-desired ‘copernican therapeutic revolution’ in small-cell lung cancer. Drugs 80:241–262
Renigunta V, Schlichthorl G, Daut J (2015) Much more than a leak: structure and function of K(2)p-channels. Pflugers Arch 467:867–894
Reynolds SD, Malkinson AM (2010) Clara cell: progenitor for the bronchiolar epithelium. Int J Biochem Cell Biol 42:1–4
Reynolds SD, Giangreco A, Power JHT, Stripp BR (2000a) Neuroepithelial bodies of pulmonary airways serve as a reservoir of progenitor cells capable of epithelial regeneration. Am J Pathol 156:269–278
Reynolds SD, Hong KU, Giangreco A, Mango GW, Guron C, Morimoto Y, Stripp BR (2000b) Conditional clara cell ablation reveals a self-renewing progenitor function of pulmonary neuroendocrine cells. Am J Physiol Lung Cell Mol Physiol 278:L1256–L1263
Riccardi D, Kemp PJ (2012) The calcium-sensing receptor beyond extracellular calcium homeostasis: conception, development, adult physiology, and disease. Annu Rev Physiol 74:271–297
Riccardi D, Finney BA, Wilkinson WJ, Kemp PJ (2009) Novel regulatory aspects of the extracellular Ca2+-sensing receptor, CaR. Pflugers Arch 458:1007–1022
Rochlitzer S, Veres TZ, Kuhne K, Prenzler F, Pilzner C, Knothe S, Winkler C, Lauenstein HD, Willart M, Hammad H, Muller M, Krug N, Lambrecht BN, Braun A (2011) The neuropeptide calcitonin gene-related peptide affects allergic airway inflammation by modulating dendritic cell function. Clin Exp Allergy 41:1609–1621
Rock JR, Onaitis MW, Rawlins EL, Lu Y, Clark CP, Xue Y, Randell SH, Hogan BL (2009) Basal cells as stem cells of the mouse trachea and human airway epithelium. Proc Natl Acad Sci U S A 106:12771–12775
Rogers DC, Haller CJ (1978) Innervation and cytochemistry of the neuroepithelial bodies in the ciliated epithelium of the toad lung (Bufo marinus). Cell Tissue Res 195:395–410
Roncalli M, Springall DR, Maggioni M, Moradoghli-Haftvani A, Winter RJD, Zhao L, Coggi G, Polak JM (1993) Early changes in the calcitonin gene-related peptide (CGRP) content of pulmonary endocrine cells concomitant with vascular remodeling in the hypoxic rat. Am J Respir Cell Mol Biol 9:467–474
Roomans GM (2010) Tissue engineering and the use of stem/progenitor cells for airway epithelium repair. Eur Cell Mater 19:284–299
Rossi G, Cavazza A, Spagnolo P, Sverzellati N, Longo L, Jukna A, Montanari G, Carbonelli C, Vincenzi G, Bogina G, Franco R, Tiseo M, Cottin V, Colby TV (2016) Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia syndrome. Eur Respir J 47:1829–1841
Saad AG, Heffelfinger S, Stanek J (2003) Amniotic sac infection syndrome features fetal lung neuroendocrine cell hyperfunction. Pediatr Dev Pathol 6:484–494
San Gabriel A, Uneyama H, Maekawa T, Torii K (2009) The calcium-sensing receptor in taste tissue. Biochem Biophys Res Commun 378:414–418
Sanderson MJ (2011) Exploring lung physiology in health and disease with lung slices. Pulm Pharmacol Ther 24:452–465
Sant’Ambrogio G, Sant'Ambrogio FB (1997) Reflexes from the upper airway, lungs, chest wall, and limbs. In: Crystal RG, West J (eds) The lung, 2nd edn. Lippincott-Raven Publishers, Philadelphia, pp 1805–1819
Sant’Ambrogio G, Widdicombe J (2001) Reflexes from airway rapidly adapting receptors. Respir Physiol 125:33–45
Schelegle ES (2003) Functional morphology and physiology of slowly adapting pulmonary stretch receptors. Anat Rec 270:11–16
Schelegle ES, Green JF (2001) An overview of the anatomy and physiology of slowly adapting pulmonary stretch receptors. Respir Physiol 125:17–31
Scheuermann DW (1987) Morphology and cytochemistry of the endocrine epithelial system in the lung. Int Rev Cytol 106:35–88
Scheuermann DW (1997) Comparative histology of pulmonary neuroendocrine cell system in mammalian lungs. Microsc Res Tech 37:31–42
Scheuermann DW, Timmermans J-P, Adriaensen D, De Groodt-Lasseel MH (1987) Immunoreactivity for calcitonin gene-related peptide in neuroepithelial bodies of the newborn cat. Cell Tissue Res 249:337–340
Schindler MB, Bohn DJ, Bryan AC, Cutz E, Rabinovitch M (1995) Increased respiratory system resistance and bronchial smooth muscle hypertrophy in children with acute postoperative pulmonary hypertension. Am J Respir Crit Care Med 152:1347–1352
Schnorbusch K, Brouns I, Lembrechts R, Pintelon I, Timmermans J-P, Adriaensen D (2012a) Functional confocal live cell imaging of the pulmonary neuroepithelial body microenvironment in GAD-GFP mice. Submitted
Schnorbusch K, Lembrechts R, Brouns I, Pintelon I, Timmermans J-P, Adriaensen D (2012b) Precision-cut vibratome slices allow functional live cell imaging of the pulmonary neuroepithelial body microenvironment in fetal mice. Adv Exp Med Biol 758:157–166
Schnorbusch K, Lembrechts R, Pintelon I, Timmermans JP, Brouns I, Adriaensen D (2013) GABAergic signaling in the pulmonary neuroepithelial body microenvironment: functional imaging in GAD67-GFP mice. Histochem Cell Biol 140:549–566
Schuller HM (1994) Carbon dioxide potentiates the mitogenic effects of nicotine and its carcinogenic derivative, NNK, in normal and neoplastic neuroendocrine lung cells via stimulation of autocrine and protein kinase C-dependent mitogenic pathways. Neurotoxicology 15:877–886
Schuller HM (2019) The impact of smoking and the influence of other factors on lung cancer. Expert Rev Respir Med 13:761–769
Schuller HM, Becker KL, Witschi HP (1988) An animal model for neuroendocrine lung cancer. Carcinogenesis 9:293–296
Schuller HM, Witschi HP, Nylen E, Joshi PA, Correa E, Becker KL (1990) Pathobiology of lung tumors induced in hamsters by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and the modulating effect of hyperoxia. Cancer Res 50:1960–1965
Schuller HM, Plummer HK III, Jull BA (2003) Receptor-mediated effects of nicotine and its nitrosated derivative NNK on pulmonary neuroendocrine cells. Anat Rec 270A:51–58
Sekhon HS, Jia Y, Raab R, Kuryatov A, Pankow JF, Whitsett JA, Lindstrom J, Spindel ER (1999) Prenatal nicotine increases pulmonary a7 nicotinic receptor expression and alters fetal lung development in monkeys. J Clin Invest 103:637–647
Shan L, Aster JC, Sklar J, Sunday ME (2007) Notch-1 regulates pulmonary neuroendocrine cell differentiation in cell lines and in transgenic mice. Am J Physiol Lung Cell Mol Physiol 292:L500–L509
Shenberger JS, Shew RL, Johnson DE (1997) Hyperoxia-induced airway remodeling and pulmonary neuroendocrine cell hyperplasia in the weaning rat. Pediatr Res 42:539–544
Sheppard BJ, Williams M, Plummer HK, Schuller HM (2000) Activation of voltage-operated Ca2+-channels in human small cell lung carcinoma by the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Int J Oncol 16:513–518
Sher E, Codignola A, Passafaro M, Tarroni P, Magnelli V, Carbone E, Clementi F (1998) Nicotinic receptors and calcium channels in small cell lung carcinoma. Functional role, modulation, and autoimmunity. Ann N Y Acad Sci 841:606–624
Shimosegawa T, Said SI (1991) Pulmonary calcitonin gene-related peptide immunoreactivity: nerve-endocrine cell interrelationships. Am J Respir Cell Mol Biol 4:126–134
Sieber C, Kopf J, Hiepen C, Knaus P (2009) Recent advances in BMP receptor signaling. Cytokine Growth Factor Rev 20:343–355
Sinha B, Biswas A, Soni GV (2018) Cellular and nuclear forces: an overview. Methods Mol Biol 1805:1–29
Smillie SJ, Brain SD (2011) Calcitonin gene-related peptide (CGRP) and its role in hypertension. Neuropeptides 45:93–104
Snyder JC, Teisanu RM, Stripp BR (2009) Endogenous lung stem cells and contribution to disease. J Pathol 217:254–264
Song H, Yao E, Lin C, Gacayan R, Chen MH, Chuang PT (2012) Functional characterization of pulmonary neuroendocrine cells in lung development, injury, and tumorigenesis. Proc Natl Acad Sci U S A 109:17531–17536
Sorhaug S, Steinshamn S, Munkvold B, Waldum HL (2008) Release of neuroendocrine products in the pulmonary circulation during intermittent hypoxia in isolated rat lung. Respir Physiol Neurobiol 162:1–7
Sorokin SP, Hoyt RF (1989) Neuroepithelial bodies and solitary small-granule cells. In: Massaro D (ed) Lung cell biology. Marcel Dekker, New York, pp 191–344
Sorokin SP, Hoyt RF (1990) On the supposed function of neuroepithelial bodies in adult mammalian lungs. News Physiol Sci 5:89–95
Sorokin SP, Hoyt RF (1993) Proceedings of workshop on pulmonary neuroendocrine cells in health and disease. Anat Rec 236:1–256
Sorokin SP, Hoyt RF, Pearsall AD (1983) Comparative biology of small granule cells and neuroepithelial bodies in the respiratory system. Am Rev Resp Dis 128:S26–S31
Sorokin SP, Hoyt RF, Shaffer MJ (1997) Ontogeny of neuroepithelial bodies: correlations with mitogenesis and innervation. Microsc Res Tech 37:43–61
Sountoulidis A, Stavropoulos A, Giaglis S, Apostolou E, Monteiro R, Chuva de Sousa Lopes SM, Chen H, Stripp BR, Mummery C, Andreakos E, Sideras P (2012) Activation of the canonical bone morphogenetic protein (BMP) pathway during lung morphogenesis and adult lung tissue repair. PLoS One 7:e41460
Springall DR, Polak JM (1993) Calcitonin gene-related peptide and pulmonary hypertension in experimental hypoxia. Anat Rec 236:96–104
Springall DR, Polak JM (1997) Quantitative microscopical methods for the identification and localisation of nerves and neuroendocrine cell markers in mammalian lung. Microsc Res Tech 37:92–100
Springall DR, Collina G, Barer G, Suggett AJ, Bee D, Polak JM (1988) Increased intracellular levels of calcitonin gene-related peptide-like immunoreactivity in pulmonary endocrine cells of hypoxic rats. J Pathol 155:259–267
Springer J, Amadesi S, Trevisani M, Harrison S, Dinh QT, McGregor GP, Fisher A, Geppetti P, Groneberg DA (2004) Effects of alpha calcitonin gene-related peptide in human bronchial smooth muscle and pulmonary artery. Regul Pept 118:127–134
Stabler CT, Morrisey EE (2017) Developmental pathways in lung regeneration. Cell Tissue Res 367:677–685
Stahlman MT, Gray ME (1984) Ontogeny of neuroendocrine cells in human fetal lung. I. An electron microscopic study. Lab Invest 51:449–463
Stahlman MT, Gray ME (1997) Immunogold EM localization of neurochemicals in human pulmonary neuroendocrine cells. Microsc Res Tech 37:77–91
Stanislawski EC, Hernandez-Garcia J, Mora-Torres MA, Abrajan-Polanco E (1981) Lung neuroendocrine structures. Topography, morphology, composition and relation with intrinsic asthma (non-immune). Arch Invest Med 12:559–577
Stevens TP, McBride JT, Peake JL, Pinkerton KE, Stripp BR (1997) Cell proliferation contributes to PNEC hyperplasia after acute airway injury. Am J Physiol 272:L486–L493
Stripp BR, Maxson K, Mera R, Singh G (1995) Plasticity of airway cell proliferation and gene expression after acute naphthalene injury. Am J Physiol 269:L791–L799
Stupnikov MR, Yang Y, Mori M, Lu J, Cardoso WV (2019) Jagged and Delta-like ligands control distinct events during airway progenitor cell differentiation. Elife 8:e50487
Suchyna TM, Johnson JH, Hamer K, Joseph FL, Gage DA, Clemo HF, Baumgarten CM, Sachs F (2000) Identification of a peptide toxin from grammostola spatulata spider venom that blocks cation-selective stretch-activated channels. J Gen Physiol 115:583–598
Sui P, Wiesner DL, Xu J, Zhang Y, Lee J, Van Dyken S, Lashua A, Yu C, Klein BS, Locksley RM, Deutsch G, Sun X (2018) Pulmonary neuroendocrine cells amplify allergic asthma responses. Science 360:eaan8546
Sullivan JP, Minna JD, Shay JW (2010) Evidence for self-renewing lung cancer stem cells and their implications in tumor initiation, progression, and targeted therapy. Cancer Metastasis Rev 29:61–72
Sun YH, Li YQ, Feng SL, Li BX, Pan ZW, Xu CQ, Li TT, Yang BF (2010) Calcium-sensing receptor activation contributed to apoptosis stimulates TRPC6 channel in rat neonatal ventricular myocytes. Biochem Biophys Res Commun 394:955–961
Sunday ME (2014) Oxygen, gastrin-releasing Peptide, and pediatric lung disease: life in the balance. Front Pediatr 2:72
Sung S, Shirazi M, Shu CA, Crapanzano JP, Saqi A (2020) Pulmonary small cell carcinoma: Review, common and uncommon differentials, genomics and management. Diagn Cytopathol
Sutherland KD, Proost N, Brouns I, Adriaensen D, Song JY, Berns A (2011) Cell of origin of small cell lung cancer: inactivation of Trp53 and Rb1 in distinct cell types of adult mouse lung. Cancer Cell 19:754–764
Tabassian AR, Nylen ES, Giron AE et al (1988) Evidence for cigarette smoke induced calcitonin secretion from lungs of man and hamster. Life Sci 42:2323–2329
Tabassian AR, Snider RH, Nylen ES, Cassidy MM, Becker KL (1993) Heterogeneity studies of hamster calcitonin following acute exposure to cigarette smoke: evidence for a monomeric secretion. Anat Rec 236:253–256
Tadokoro T, Gao X, Hong CC, Hotten D, Hogan BL (2016) BMP signaling and cellular dynamics during regeneration of airway epithelium from basal progenitors. Development 143:764–773
Tamamaki N, Yanagawa Y, Tomioka R, Miyazaki J, Obata K, Kaneko T (2003) Green fluorescent protein expression and colocalization with calretinin, parvalbumin, and somatostatin in the GAD67-GFP knock-in mouse. J Comp Neurol 467:60–79
Taylor-Clark T, Undem BJ (2006) Transduction mechanisms in airway sensory nerves. J Appl Physiol 101:950–959
Teisanu RM, Chen H, Matsumoto K, McQualter JL, Potts E, Foster WM, Bertoncello I, Stripp BR (2011) Functional analysis of two distinct bronchiolar progenitors during lung injury and repair. Am J Respir Cell Mol Biol 44:794–803
Thebaud B, Ladha F, Michelakis ED, Sawicka M, Thurston G, Eaton F, Hashimoto K, Harry G, Haromy A, Korbutt G, Archer SL (2005) Vascular endothelial growth factor gene therapy increases survival, promotes lung angiogenesis, and prevents alveolar damage in hyperoxia-induced lung injury: evidence that angiogenesis participates in alveolarization. Circulation 112:2477–2486
Tjen-A-Looi S, Kraiczi H, Ekman R, Keith IM (1998) Sensory CGRP depletion by capsaicin exacerbates hypoxia-induced pulmonary hypertension in rats. Regul Pept 74:1–10
Tsao PN, Vasconcelos M, Izvolsky KI, Qian J, Lu J, Cardoso WV (2009) Notch signaling controls the balance of ciliated and secretory cell fates in developing airways. Development 136:2297–2307
Tsutsumi Y, Osamura RY, Watanabe K, Yanaihara N (1983) Immunohistochemical studies on gastrin-releasing peptide- and adrenocorticotropic hormone-containing cells in the human lung. Lab Invest 48:623–632
Uddman R, Luts A, Sundler F (1985) Occurrence and distribution of calcitonin gene-related peptide in the mammalian respiratory tract and middle ear. Cell Tissue Res 241:551–555
Umans BD, Liberles SD (2018) Neural sensing of organ volume. Trends Neurosci 41:911–924
Undem BJ, Sun H (2020) Molecular/ionic basis of vagal bronchopulmonary C-Fiber activation by inflammatory mediators. Physiology (Bethesda) 35:57–68
Van Genechten J, Brouns I, Burnstock G, Timmermans J-P, Adriaensen D (2004) Quantification of neuroepithelial bodies and their innervation in Fawn-Hooded and Wistar rat lungs. Am J Respir Cell Mol Biol 30:20–30
Van Lommel A (2001) Pulmonary neuroendocrine cells (PNEC) and neuroepithelial bodies (NEB): chemoreceptors and regulators of lung development. Paediatr Respir Rev 2:171–176
Van Lommel A, Lauweryns JM (1993) Neuroepithelial bodies in the Fawn Hooded rat lung: morphological and neuroanatomical evidence for a sensory innervation. J Anat 183:553–566
Vaughan AE, Chapman HA (2013) Regenerative activity of the lung after epithelial injury. Biochim Biophys Acta 1832:922–930
Vaughan AE, Brumwell AN, Xi Y, Gotts JE, Brownfield DG, Treutlein B, Tan K, Tan V, Liu FC, Looney MR, Matthay MA, Rock JR, Chapman HA (2015) Lineage-negative progenitors mobilize to regenerate lung epithelium after major injury. Nature 517:621–625
Verástegui C, Oliveira AP, Fernández-Vivero J, Romero A, de Castro JM (1997) Calcitonin gene-related peptide immunoreactivity in adult mouse lung. Eur J Histochem 41:119–126
Verckist L, Lembrechts R, Thys S, Pintelon I, Timmermans JP, Brouns I, Adriaensen D (2017) Selective gene expression analysis of the neuroepithelial body microenvironment in postnatal lungs with special interest for potential stem cell characteristics. Respir Res 18:87
Verckist L, Pintelon I, Timmermans JP, Brouns I, Adriaensen D (2018) Selective activation and proliferation of a quiescent stem cell population in the neuroepithelial body microenvironment. Respir Res 19:207
Vernooy JHJD, Dentener MA, van Suylen RJ, Buurman WA, Wouters EFM (2001) Intratracheal instillation of lipopolysaccharide in mice induces apoptosis in bronchial epithelial cells. Am J Respir Cell Mol Biol 24:569–576
Viana F, de la Pena E, Pecson B, Schmidt RF, Belmonte C (2001) Swelling-activated calcium signalling in cultured mouse primary sensory neurons. Eur J Neurosci 13:722–734
Volckaert T, De Langhe SP (2015) Wnt and FGF mediated epithelial-mesenchymal crosstalk during lung development. Dev Dyn 244:342–366
Wang D, Youngson CR, Wong V, Yeger H, Dinauer MC, Vega-Saenz ME, Rudy B, Cutz E (1996) NADPH-oxidase and a hydrogen peroxide-sensitive K+ channel may function as an oxygen sensor complex in airway chemoreceptors and small cell lung carcinoma cell lines. Proc Natl Acad Sci USA 93:13182–13187
Wang F, Knutson K, Alcaino C, Linden DR, Gibbons SJ, Kashyap P, Grover M, Oeckler R, Gottlieb PA, Li HJ, Leiter AB, Farrugia G, Beyder A (2017) Mechanosensitive ion channel Piezo2 is important for enterochromaffin cell response to mechanical forces. J Physiol 595:79–91
Wang HY, Owens JD, Shih JH, Li MC, Bonner RF, Mushinski JF (2006) Histological staining methods preparatory to laser capture microdissection significantly affect the integrity of the cellular RNA. BMC Genomics 7:97
Wang RN, Green J, Wang Z, Deng Y, Qiao M, Peabody M, Zhang Q, Ye J, Yan Z, Denduluri S, Idowu O, Li M, Shen C, Hu A, Haydon RC, Kang R, Mok J, Lee MJ, Luu HL, Shi LL (2014) Bone morphogenetic protein (BMP) signaling in development and human diseases. Genes Dis 1:87–105
Wang Y, Chandra R, Samsa LA, Gooch B, Fee BE, Cook JM, Vigna SR, Grant AO, Liddle RA (2011) Amino acids stimulate cholecystokinin release through the Ca2+-sensing receptor. Am J Physiol Gastrointest Liver Physiol 300:G528–G537
Wansleeben C, Barkauskas CE, Rock JR, Hogan BL (2013) Stem cells of the adult lung: their development and role in homeostasis, regeneration, and disease. Wiley interdisciplinary reviews. Dev Biol 2:131–148
Wasano K (1977) Neuroepithelial bodies in the lung of rat and mouse. Arch Histol Jpn 40:207–219
Wasano K, Yamamoto T (1978) Monoamine-containing granulated cells in the frog lung. Cell Tissue Res 193:201–209
Watanabe N, Horie S, Michael GJ, Spina D, Page CP, Priestley JV (2005) Immunohistochemical localization of vanilloid receptor subtype 1 (TRPV1) in the guinea pig respiratory system. Pulm Pharmacol Ther 18:187–197
West PW, Canning BJ, Merlo-Pich E, Woodcock AA, Smith JA (2015) Morphologic characterization of nerves in whole-mount airway biopsies. Am J Respir Crit Care Med 192:30–39
Wharton J, Polak JM, Bloom SR, Ghatei MA, Solcia E, Brown MR, Pearse AG (1978) Bombesin-like immunoreactivity in the lung. Nature 273:769–770
White SR, Hershenson MB, Sigrist KS, Zimmermann A, Solway J (1993) Proliferation of guinea-pig tracheal epithelial cells induced by calcitonin gene-related peptide. Am J Respir Cell Mol Biol 8:592–596
Whitsett JA, Kalin TV, Xu Y, Kalinichenko VV (2019) Building and Regenerating the lung cell by cell. Physiol Rev 99:513–554
Widdicombe J (1986) The neural reflexes in the airways. Eur J Respir Dis Suppl 144:1–3
Widdicombe J (2003) Functional morphology and physiology of pulmonary rapidly adapting receptors (RARs). Anat Rec 270:2–10
Widdicombe J (2006) Reflexes from the lungs and airways: historical perspective. J Appl Physiol 101:628–634
Widdicombe J (2009) Lung afferent activity: Implications for respiratory sensation. Respir Physiol Neurobiol 167:2–8
Widdicombe JG (2001) Airway receptors. Respir Physiol 125:3–15
Williams EK, Chang RB, Strochlic DE, Umans BD, Lowell BB, Liberles SD (2016) Sensory neurons that detect stretch and nutrients in the digestive system. Cell 166:209–221
Winkelmann A, Noack T (2010) The clara cell: a “Third Reich eponym”? Eur Respir J 36:722–727
Wistuba II, Gazdar AF, Minna JD (2001) Molecular genetics of small cell lung carcinoma. Semin Oncol 28:3–13
Wolf P, Hall C, Kilbourn JP (1986) Demonstration of calcitonin and calmodulin by immunoperoxidase in the cystic fibrosis lung. Chest 89:327–330
Wu J, Lewis AH, Grandl J (2017) Touch, tension, and transduction—the function and regulation of Piezo Ion channels. Trends Biochem Sci 42:57–71
Wuenschell CW, Sunday ME, Singh G, Minoo P, Slavkin HC, Warburton D (1996) Embryonic mouse lung epithelial progenitor cells co-express immunohistochemical markers of diverse mature cell lineages. J Histochem Cytochem 44:113–123
Xu K, Nieuwenhuis E, Cohen BL, Wang W, Canty AJ, Danska JS, Coultas L, Rossant J, Wu MY, Piscione TD, Nagy A, Gossler A, Hicks GG, Hui CC, Henkelman RM, Yu LX, Sled JG, Gridley T, Egan SE (2010) Lunatic Fringe-mediated Notch signaling is required for lung alveogenesis. Am J Physiol Lung Cell Mol Physiol 298:L45–L56
Yabumoto Y, Watanabe M, Ito Y, Maemura K, Otsuki Y, Nakamura Y, Yanagawa Y, Obata K, Watanabe K (2008) Expression of GABAergic system in pulmonary neuroendocrine cells and airway epithelial cells in GAD67-GFP knock-in mice. Med Mol Morphol 41:20–27
Yao E, Lin C, Wu Q, Zhang K, Song H, Chuang PT (2018) Notch signaling controls transdifferentiation of pulmonary neuroendocrine cells in response to lung injury. Stem Cells 36:377–391
Yarova PL, Stewart AL, Sathish V, Britt RD, Jr., Thompson MA, Lowe APP, Freeman M, Aravamudan B, Kita H, Brennan SC, Schepelmann M, Davies T, Yung S, Cholisoh Z, Kidd EJ, Ford WR, Broadley KJ, Rietdorf K, Chang W, Bin Khayat ME, Ward DT, Corrigan CJ, Ward JPT, Kemp PJ, Pabelick CM, Prakash YS, Riccardi D (2015) Calcium-sensing receptor antagonists abrogate airway hyperresponsiveness and inflammation in allergic asthma. Sci Transl Med 7:284ra260
Young LR, Brody AS, Inge TH, Acton JD, Bokulic RE, Langston C, Deutsch GH (2011) Neuroendocrine cell distribution and frequency distinguish neuroendocrine cell hyperplasia of infancy from other pulmonary disorders. Chest 139:1060–1071
Youngson C, Nurse C, Yeger H, Cutz E (1993) Oxygen sensing in airway chemoreceptors. Nature 365:153–155
Youngson C, Nurse C, Yeger H, Curnutte JT, Vollmer C, Wong V, Cutz E (1997) Immunocytochemical localization on O2-sensing protein (NADPH oxidase) in chemoreceptor cells. Microsc Res Tech 37:101–106
Yu J (2002) An overview of vagal airway receptors. Acta Physiol Sinica 54:451–459
Yu J (2005) Airway mechanosensors. Respir Physiol Neurobiol 148:243
Yu J (2009) Airway Receptors and Their Reflex Function. In: Gonzalez C, Nurse CA, Peers C (eds) Arterial Chemoreceptors. Advances in Experimental Medicine and Biology, vol 648. Springer, Dordrecht, pp 411–420
Yu J, Zhang J (2004) A single pulmonary mechano-sensory unit possesses multiple encoders in rabbits. Neurosci Lett 362:171–175
Yu J, Wang YF, Zhang JW (2003) Structure of slowly adapting pulmonary stretch receptors in the lung periphery. J Appl Physiol 95:385–393
Yu J, Zhang J, Wang Y, Fan F, Yu A (2004) Neuroepithelial bodies not connected to pulmonary slowly adapting stretch receptors. Respir Physiol Neurobiol 144:1–14
Zeng F, Xu S-Z, Jackson PK, Mchugh D, Kumar B, Fountain SJ, Beech DJ (2004) Human TRPC5 channel activated by a multiplicity of signals in a single cell. J Physiol 559(3):739–750
Zhang JW, Walker JF, Guardiola J, Yu J (2006) Pulmonary sensory and reflex responses in the mouse. J Appl Physiol 101:986–992
Zhao H, Sprunger KL, Simasko MS (2010a) Expression of transient receptor potential channels and two-pore potassium channels in subtypes of vagal afferent neurons in rat. Am J Physiol Gastrointest Liver Physiol 298:212–221
Zhao S, Zhou Y, Gross J, Miao P, Qiu L, Wang D, Chen Q, Feng G (2010b) Fluorescent labeling of newborn dentate granule cells in GAD67-GFP transgenic mice: a genetic tool for the study of adult neurogenesis. PLoS One 5:e12506
Zhao Q, Wang W, Wang R, Cheng Y (2016) TRPV1 and neuropeptide receptor immunoreactivity and expression in the rat lung and brainstem after lung ischemia-reperfusion injury. J Surg Res 203:183–192
Conflict of Interest
Inge Brouns, Line Verckist, Isabel Pintelon, Jean-Pierre Timmermans, and Dirk Adriaensen declare that they have no conflict of interest.
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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
This work is a review of previously published accounts, as such, no human studies were performed.
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Brouns, I., Verckist, L., Pintelon, I., Timmermans, JP., Adriaensen, D. (2021). The Pulmonary Neuroepithelial Body Microenvironment: A Multifunctional Unit in the Airway Epithelium. In: The Pulmonary Neuroepithelial Body Microenvironment . Advances in Anatomy, Embryology and Cell Biology, vol 233. Springer, Cham. https://doi.org/10.1007/978-3-030-65817-5_1
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