Skip to main content

Neurochemical Anatomy of the Mammalian Carotid Body

  • Chapter
  • First Online:
Morphofunctional and Neurochemical Aspects of the Mammalian Carotid Body

Abstract

Carotid body (CB) glomus cells in most mammals, including humans, contain a broad diversity of classical neurotransmitters, neuropeptides and gaseous signaling molecules as well as their cognate receptors. Among them, acetylcholine, adenosine triphosphate and dopamine have been proposed to be the main excitatory transmitters in the mammalian CB, although subsequently dopamine has been considered an inhibitory neuromodulator in almost all mammalian species except the rabbit. In addition, co-existence of biogenic amines and neuropeptides has been reported in the glomus cells, thus suggesting that they store and release more than one transmitter in response to natural stimuli. Furthermore, certain metabolic and transmitter-degrading enzymes are involved in the chemotransduction and chemotransmission in various mammals. However, the presence of the corresponding biosynthetic enzyme for some transmitter candidates has not been confirmed, and neuroactive substances like serotonin, gamma-aminobutyric acid and adenosine, neuropeptides including opioids, substance P and endothelin, and gaseous molecules such as nitric oxide have been shown to modulate the chemosensory process through direct actions on glomus cells and/or by producing tonic effects on CB blood vessels. It is likely that the fine balance between excitatory and inhibitory transmitters and their complex interactions might play a more important than suggested role in CB plasticity.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Alcayaga C, Varas R, Valdés V, Carpa V, Arroyo J, Iturriaga R, Alcayaga J (2006) ATP- and ACh-induced responses in isolated cat petrosal ganglion neurons. Brain Res 1131:60–67

    Article  PubMed  Google Scholar 

  • Alfes H, Kindler J, Knoche H, Matthiessen D, Möllmann H, Pagnucco R (1977) The biogenic amines in the carotid body. Prog Histochem Cytochem 10:1–69

    CAS  PubMed  Google Scholar 

  • Allen AM (1998) Angiotensin AT1 receptor-mediated excitation of rat carotid body 1981chemoreceptor afferent activity. J Physiol 510:773–781

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Almaraz L, Pérez-García MT, Gómez-Nino A, González C (1997) Mechanisms of α2-adrenoceptor-mediated inhibition in rabbit carotid body. Am J Physiol 272:628–637

    Article  Google Scholar 

  • Armengaud C, Leitner LM, Malber CH, Roumy M, Ruckebusch M, Sutra JF (1988) Comparison of the monoamine and catabolite content in the cat and rabbit carotid bodies. Neurosci Lett 85:153–157

    Article  CAS  PubMed  Google Scholar 

  • Atanasova DY, Lazarov NE (2012) Expression of some neuropeptides in the rat carotid body. Acta Morphol Anthropol 19:15–19

    Google Scholar 

  • Atanasova DY, Lazarov NE (2015) Histochemical demonstration of tripeptidyl aminopeptidase I in the rat carotid body. Acta Histochem 117:219–222

    Article  CAS  PubMed  Google Scholar 

  • Atanasova DY, Dimitrov ND, Lazarov NE (2016a) Expression of nitric oxide-containing structures in the rat carotid body. Acta Histochem 118:770–775

    Article  CAS  PubMed  Google Scholar 

  • Atanasova D, Dimitrov N, Dandov A, Lazarov NE (2016b) CGRP- and VIP-immunoreactivity in the rat carotid body. Acta Morphol Anthropol 23:16–21

    Google Scholar 

  • Atanasova D, Dandov A, Dimitrov N, Lazarov NE (2018) Immunohistochemical localization of angiotensin AT1 receptors in the rat carotid body. Acta Histochem 120:154–158

    Article  CAS  PubMed  Google Scholar 

  • Baby SM, Zaidi F, Hunsberger GE, Sokal D, Gupta I, Conde SV, Chew D, Rall K, Coatney RW (2023) Acute effects of insulin and insulin-induced hypoglycaemia on carotid body chemoreceptor activity and cardiorespiratory responses in dogs. Exp Physiol 108:280–295

    Article  CAS  PubMed  Google Scholar 

  • Badoer E (2020) The carotid body a common denominator for cardiovascular and metabolic dysfunction? Front Physiol 11:1069

    Article  PubMed  PubMed Central  Google Scholar 

  • Ballard KJ, Jones JV (1971) The fine structural localization of cholinesterases in the carotid body of the cat. J Physiol 219:747–753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ballard KJ, Jones JV (1972) Demonstration of choline acetyltransferase activity in the carotid body of the cat. J Physiol Lond 227:87–94

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bin-Jaliah I, Maskell PD, Kumar P (2004) Indirect sensing of insulin-induced hypoglycaemia by the carotid body in the rat. J Physiol 556:255–266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Biscoe TJ, Silver A (1966) The distribution of cholinesterases in the cat carotid body. J Physiol 183:501–512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Böck P (1980) Adenine nucleotides in the carotid body. Cell Tissue Res 206:279–290

    Article  PubMed  Google Scholar 

  • Böck P, Gorgas K (1976) Catecholamines and granule content of carotid body type I cells. In: Coupland RE, Fujita T (eds) Chromaffin, enterochromaffin and related cells. Elsevier, Amsterdam–Oxford–New York, pp 355–374

    Google Scholar 

  • Bolme P, Fuxe K, Hökfelt T, Goldstein M (1977) Studies on the role of dopamine in cardiovascular and respiratory control: central versus peripheral mechanisms. Adv Biochem Psychopharmacol 16:281–290

    CAS  PubMed  Google Scholar 

  • Buckler KJ (2012) Effects of exogenous hydrogen sulphide on calcium signalling, background (TASK) K channel activity and mitochondrial function in chemoreceptor cells. Pflügers Arch 463:743–754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Buttigieg J, Nurse CA (2004) Detection of hypoxia-evoked ATP release from chemoreceptor cells of the rat carotid body. Biochem Biophys Res Commun 322:82–87

    Article  CAS  PubMed  Google Scholar 

  • Caballero-Eraso C, Shin M-K, Pho H, Kim LJ, Pichard LE, Wu Z-J, Gu C, Berger S, Pham L, Yeung H-Y, Shirahata M, Schwartz AR, Tang W-Y, Sham JSK, Polotsky VY (2019) Leptin acts in the carotid bodies to increase minute ventilation during wakefulness and sleep and augment the hypoxic ventilatory response. J Physiol 597:151–172

    Article  CAS  PubMed  Google Scholar 

  • Campanucci VA, Nurse CA (2007) Autonomic innervation of the carotid body: role in efferent inhibition. Respir Physiol Neurobiol 157:83–92

    Article  CAS  PubMed  Google Scholar 

  • Campanucci VA, Zhang M, Vollmer C, Nurse CA (2006) Expression of multiple P2X receptors by glossopharyngeal neurons projecting to rat carotid body O2-chemoreceptors: role in nitric oxide-mediated efferent inhibition. J Neurosci 26:9482–9493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Campanucci VA, Dookhoo L, Vollmer C, Nurse CA (2012) Modulation of the carotid body sensory discharge by NO: an up-dated hypothesis. Respir Physiol Neurobiol 184:149–157

    Article  CAS  PubMed  Google Scholar 

  • Chen IL, Hansen JT, Yates RD (1985) Dopamine beta hydroxylase-like immunoreactivity in the rat and cat carotid body: a light and electron microscopic study. J Neurocytol 14:131–144

    Article  CAS  PubMed  Google Scholar 

  • Chen IL, Yates RD, Hansen JT (1986) Substance P-like immunoreactivity in rat and cat carotid bodies: light and electron microscopic studies. Histol Histopathol 1:203–212

    CAS  PubMed  Google Scholar 

  • Chen J, He L, Dinger B, Fidone S (2000a) Cellular mechanisms involved in rabbit carotid body excitation elicited by endothelin peptides. Respir Physiol 121:13–23

    Article  CAS  PubMed  Google Scholar 

  • Chen J, He L, Dinger B, Fidone S (2000b) Pharmacological effects of endothelin in rat carotid body. activation of second messenger pathways and potentiation of chemoreceptor activity. Adv Exp Med Biol 475:517–525

    Article  CAS  PubMed  Google Scholar 

  • Chen J, He L, Dinger B, Stensaas L, Fidone S (2002) Role of endothelin and endothelin A-type receptor in adaptation of the carotid body to chronic hypoxia. Am J Physiol Lung Cell Mol Physiol 282:L1314–L1323

    Article  CAS  PubMed  Google Scholar 

  • Conde SV, Monteiro EC (2004) Hypoxia induces adenosine release from the rat carotid body. J Neurochem 89:1148–1156

    Article  CAS  PubMed  Google Scholar 

  • Conde SV, Monteiro EC (2006) Profiles for ATP and adenosine release at the carotid body in response to O2 concentrations. Adv Exp Med Biol 580:179–184

    Article  CAS  PubMed  Google Scholar 

  • Conde SV, González C, Batuca JR, Monteiro EC, Obeso A (2008) An antagonistic interaction between A2B adenosine and D2 dopamine receptors modulates the function of rat carotid body chemoreceptor cells. J Neurochem 107:1369–1381

    Article  CAS  PubMed  Google Scholar 

  • Conde SV, Monteiro EC, Obeso A, González C (2009) Adenosine in peripheral chemoreception: new insights into a historically overlooked molecule. In: González C, Nurse CA, Peers C (eds) Arterial chemoreceptors, vol 648. Springer Science+Business Media BV, Dordrecht, pp 145–159

    Google Scholar 

  • Conde SV, Sacramento JF, Guarino MP, González C, Obeso A, Diogo LN, Monteiro EC, Ribeiro MJ (2014) Carotid body, insulin, and metabolic diseases: unraveling the links. Front Physiol 5:418

    Article  PubMed  PubMed Central  Google Scholar 

  • Conde SV, Monteiro EC, Sacramento JF (2017) Purines and carotid body: new roles in pathological conditions. Front Pharmacol 8:913

    Article  PubMed  PubMed Central  Google Scholar 

  • Conde SV, Sacramento JF, Guarino MP (2018) Carotid body: a metabolic sensor implicated in insulin resistance. Physiol Genomics 50:208–214

    Article  CAS  PubMed  Google Scholar 

  • Cragg PA, Runold M, Kou YR, Prabkakar NR (1994) Tachykinin antagonists in carotid body responses to hypoxia and substance P in the rat. Respir Physiol 95:295–310

    Article  CAS  PubMed  Google Scholar 

  • Cuello AC, McQueen DS (1980) Substance P: a carotid body peptide. Neurosci Lett 17:215–219

    Article  CAS  PubMed  Google Scholar 

  • Czyzyk-Krzeska MF, Lawson EE, Millhorn DE (1992) Expression of D2 dopamine receptor mRNA in the arterial chemoreceptor afferent pathway. J Auton Nerv Syst 41:31–39

    Article  CAS  PubMed  Google Scholar 

  • Dawson TM, Bredt DS, Fotuhi M, Hwang PM, Snyder SH (1991) Nitric oxide synthase and neuronal NADPH diaphorase are identical in brain and peripheral tissues. Proc Natl Acad Sci USA 88:7797–7801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Del Rio R, Moya EA, Koenig CS, Fujiwara K, Alcayaga J, Iturriaga R (2008) Modulatory effects of histamine on cat carotid body chemoreception. Respir Physiol Neurobiol 164:401–410

    Article  PubMed  Google Scholar 

  • Del Rio R, Moya EA, Alcayaga J, Iturriaga R (2009) Evidence for histamine as a new modulator of carotid body chemoreception. Adv Exp Med Biol 648:177–184

    Article  PubMed  Google Scholar 

  • Di Giulio C, Marconi GD, Zara S, Di Tano A, Porzionato A, Pokorski M, Cataldi A, Mazzatenta A (2015) Selective expression of galanin in neuronal-like cells of human carotid body. Adv Exp Med Biol 860:315–323

    Article  PubMed  Google Scholar 

  • Donnelly DF (1996) Chemoreceptor nerve excitation may be not proportional to catecholamine secretion. J Appl Physiol 81:2330–2337

    Article  Google Scholar 

  • Douglas WW (1954) Is there chemical transmission at chemoreceptors? Pharmacol Rev 6:81–83

    CAS  PubMed  Google Scholar 

  • Eyzaguirre C, Zapata P (1968) The release of acetylcholine from carotid body tissue. Further study on the effects of acetylcholine and cholinergic blocking agents on the chemosensory discharge. J Physiol Lond 195:589–607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fearon IM, Zhang M, Vollmer C, Nurse CA (2003) GABA mediates autoreceptor feedback inhibition in the rat carotid body via presynaptic GABAB receptors and TASK-1. J Physiol 553:83–94

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fidone SJ, González C (1986) Initiation and control of chemoreceptor activity in the carotid body. In: Fishman AP, Cherniack NS, Widdicombe JG (eds) Handbook of physiology, vol 2. American Physiological Society, Bethesda, pp 247–312

    Google Scholar 

  • Fidone S, González C, Yoshizaki K (1982) Effects of hypoxia on catecholamine synthesis in rabbit carotid body in vitro. J Physiol 333:81–91

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fidone SJ, González C, Dinger BG, Hanson GR (1988) Mechanisms of chemotransmission in the mammalian carotid body. Prog Brain Res 74:169–179

    Article  CAS  PubMed  Google Scholar 

  • Finley JC, Erickson JT, Katz DM (1995) Galanin expression in carotid body afferent neurons. Neuroscience 68:937–942

    Article  CAS  PubMed  Google Scholar 

  • Fitzgerald RS (2000) Oxygen and carotid body chemotransduction: the cholinergic hypothesis—a brief history and new evaluation. Resp Physiol 120:89–104

    Article  CAS  Google Scholar 

  • Fitzgerald RS, Shirahata M, Wang HY, Balbir A, Chang I (2004) The impact of adenosine on the release of acetylcholine, dopamine, and norepinephrine from the cat carotid body. Neurosci Lett 367:304–308

    Article  CAS  PubMed  Google Scholar 

  • Fitzgerald RS, Eyzaguirre C, Zapata P (2009a) Fifty years of progress in carotid body physiology. In: González C, Nurse CA, Peers C (eds) Arterial chemoreceptors. Advances in experimental medicine and biology, vol 648. Springer, Dordrecht, pp 19–28

    Google Scholar 

  • Fitzgerald RS, Shirahata M, Chang I, Kostuk E (2009b) The impact of hypoxia and low glucose on the release of acetylcholine and ATP from the incubated cat carotid body. Brain Res 1270:39–44

    Article  CAS  PubMed  Google Scholar 

  • Fitzgerald RS, Shirahata M, Chang I, Kostuk E, Kiihl S (2011) The impact of hydrogen sulfide (H2S) on neurotransmitter release from the cat carotid body. Respir Physiol Neurobiol 176:80–89

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fung ML (2015) Expressions of angiotensin and cytokine receptors in the paracrine signaling of the carotid body in hypoxia and sleep apnea. Respir Physiol Neurobiol 209:6–12

    Article  CAS  PubMed  Google Scholar 

  • Fung ML, Lam SY, Chen Y, Dong X, Leung PS (2001) Functional expression of angiotensin II receptors in type-I cells of the rat carotid body. Pflügers Arch 441:474–480

    Article  CAS  PubMed  Google Scholar 

  • Gauda EB (2002) Gene expression in peripheral arterial chemoreceptors. Microsc Res Tech 59:153–167

    Article  CAS  PubMed  Google Scholar 

  • Gauda EB, Northington FJ, Linden J, Rosin DL (2000) Differential expression of A2A, A1-adenosine and D2-dopamine receptor genes in rat peripheral arterial chemoreceptors during postnatal development. Brain Res 872:1–10

    Article  CAS  PubMed  Google Scholar 

  • Gonkowski S (2020) Vasoactive intestinal polypeptide in the carotid body—a history of forty years of research. A mini review. Int J Mol Sci 21:4692

    Google Scholar 

  • González C, Kwok Y, Gibb J, Fidone S (1981) Physiological and pharmacological effects on TH activity in rabbit and cat carotid body. Am J Physiol 240:R38–R43

    PubMed  Google Scholar 

  • González C, Almaraz L, Obeso A, Rigual R (1994) Carotid body chemoreceptors: from natural stimuli to sensory discharges. Physiol Rev 74:829–898

    Article  PubMed  Google Scholar 

  • Grimes PA, Mokashi A, Stone R, Lahiri S (1995) Nitric oxide synthase in autonomic innervation of the cat carotid body. J Auton Nerv Syst 54:80–86

    Article  CAS  PubMed  Google Scholar 

  • Grönblad M, Liesi P, Rechardt L (1983) Serotonin-like immunoreactivity in rat carotid body. Brain Res 276:348–350

    Article  PubMed  Google Scholar 

  • Hansen JT, Brokaw J, Christie D, Karasek M (1982) Localization of enkephalin-like immunoreactivity in the cat carotid and aortic body chemoreceptors. Anat Rec 203:405–410

    Article  CAS  PubMed  Google Scholar 

  • Hanson G, Jones L, Fidone S (1986) Physiological chemoreceptor stimulation decreases enkephalin and substance P in the carotid body. Peptides 7:767–769

    Article  CAS  PubMed  Google Scholar 

  • He L, Chen J, Dinger B, Stensaas L, Fidone S (1996) Endothelin modulates chemoreceptor cell function in mammalian carotid body. Adv Exp Med Biol 410:305–311

    Article  CAS  PubMed  Google Scholar 

  • Heath D, Quinzanini M, Rodella A, Albertini A, Ferrari R, Harris P (1988) Immunoreactivity to various peptides in the human carotid body. Res Commun Chem Pathol Pharmacol 62:289–293

    CAS  PubMed  Google Scholar 

  • Helke CJ, O’Donohue TL, Jacobowitz DM (1980) Substance P as a baro- and chemoreceptor afferent neurotransmitter: immunocytochemical and neurochemical evidence in the rat. Peptides 1:1–9

    Article  CAS  PubMed  Google Scholar 

  • Hess A (1978) Are glomus cells in the rat carotid body dopaminergic or noradrenergic? Neuroscience 3:413–418

    Article  CAS  PubMed  Google Scholar 

  • Heym C, Kummer W (1989) Immunohistochemical distribution and colocalization of regulatory peptides in the carotid body. J Electron Microsc Tech 12:331–342

    Article  CAS  PubMed  Google Scholar 

  • Heym C, Triepel J (1985) Immunohistochemical localization of vasoactive intestinal polypeptide in the mammalian central and peripheral nervous systems. In: Parvez H, Parvez S, Gupta D (eds) Neuroendocrinology of hormone-transmitter interactions. VNU International Science Press, Utrecht, pp 99–125

    Google Scholar 

  • Höhler B, Mayer B, Kummer W (1994) Nitric oxide synthase in the rat carotid body and carotid sinus. Cell Tissue Res 276:559–564

    Article  PubMed  Google Scholar 

  • Hollinshead WH, Sawyer CH (1945) Mechanisms of carotid body stimulation. Am J Physiol 122:79–86

    Article  Google Scholar 

  • Holmes AP, Kumar P (2023) Low sugar and the drive to breathe: is insulin another adequate stimulus for the carotid body? Exp Physiol 108:167–168

    Article  CAS  PubMed  Google Scholar 

  • Hope BT, Michael GJ, Knigge KM, Vincent SR (1991) Neuronal NADPH diaphorase is a nitric oxide synthase. Proc Natl Acad Sci USA 88:2811–2814

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huey KA, Szewczak JM, Powell FL (2003) Dopaminergic mechanisms of neural plasticity in respiratory control: transgenic approaches. Respir Physiol Neurobiol 135:133–144

    Google Scholar 

  • Ichikawa H (2002) Innervation of the carotid body: immunohistochemical, denervation, and retrograde tracing studies. Misrosc Res Tech 59:188–195

    Google Scholar 

  • Ichikawa H, Helke CJ (1993) Distribution, origin and plasticity of galanin-immunoreactivity in the rat carotid body. Neuroscience 52:757–767

    Article  CAS  PubMed  Google Scholar 

  • Ichikawa H, Helke CJ (1995) Parvalbumin and calbindin D-28k in vagal and glossopharyngeal sensory neurons of the rat. Brain Res 675:337–341

    Google Scholar 

  • Ichikawa H, Helke CJ (1997) Coexistence of calcium-binding proteins in vagal and glossopharyngeal sensory neurons of the rat. Brain Res 768:349–353

    Article  CAS  PubMed  Google Scholar 

  • Ichikawa H, Jacobowitz DM, Winsky L, Helke CJ (1991) Calretinin-immunoreactivity in vagal and glossopharyngeal sensory neurons of the rat: distribution and coexistence with putative transmitter agents. Brain Res 557:316–321

    Article  CAS  PubMed  Google Scholar 

  • Ichikawa H, Schulz S, Höllt V, Sugimoto T (2005) Delta-opioid receptor-immunoreactive neurons in the rat cranial sensory ganglia. Brain Res 1043:225–230

    Article  CAS  PubMed  Google Scholar 

  • Igarashi A, Zadzilka N, Shirahata M (2009) Benzodiazepines and GABA-GABAA receptor system in the cat carotid body. Adv Exp Med Biol 648:169–175

    Article  CAS  PubMed  Google Scholar 

  • Ishizawa Y, Fitzgerald RS, Shirahata M, Schofield B (1996) Localization of nicotinic acetylcholine receptors in cat carotid body and petrosal ganglion. In: Zapata P, Eyzaguirre C, Torrance R (eds) Frontiers in arterial chemoreception, vol 410. Plenum Press, London, pp 253–256

    Chapter  Google Scholar 

  • Iturriaga R, Alcayaga J (2004) Neurotransmission in the carotid body: transmitters and modulators between glomus cells and petrosal ganglion nerve terminals. Brain Res Rev 47:46–53

    Article  CAS  PubMed  Google Scholar 

  • Iturriaga R, Alcayaga J, González C (2009) Neurotransmitters in carotid body function: the case of dopamine. In: González C, Nurse CA, Peers C (eds) Arterial chemoreceptors, vol 648. Springer Science+Business Media BV, Dordrecht, pp 137–144

    Google Scholar 

  • Jacobowitz DM, Helke CJ (1980) Localization of substance P immunoreactive nerves in the carotid body. Brain Res Bull 5:195–197

    Article  CAS  PubMed  Google Scholar 

  • Jacono FJ, Peng YJ, Kumar GK, Prabhakar NR (2005) Modulation of the hypoxic sensory response of the carotid body by 5-hydroxytryptamine: role of the 5-HT2 receptor. Respir Physiol Neurobiol 145:135–142

    Article  CAS  PubMed  Google Scholar 

  • Jones JV (1975) Localization and quantitation of the carotid body enzymes: their relevance to the cholinergic transmitter hypothesis. In: Purves MJ (ed) The peripheral arterial chemoreceptors. Cambridge University Press, London, pp 143–162

    Google Scholar 

  • Jonsson M, Lindahl S, Eriksson L (2005) Effect of propofol on carotid body chemosensitivity and cholinergic chemotransduction. Anesthesiology 102:110–116

    Article  CAS  PubMed  Google Scholar 

  • Kameda Y (1989) Distribution of CGRP-, somatostatin-, galanin-, VIP-, and substance P-immunoreactive nerve fibers in the chicken carotid body. Cell Tissue Res 257:623–629

    Article  CAS  PubMed  Google Scholar 

  • Kameda Y (1998) Substance P- and CGRP-immunoreactive fibers in the chicken carotid bodies after nodose ganglionectomy and midcervical vagotomy. Brain Res 807:246–249

    Article  CAS  PubMed  Google Scholar 

  • Kameda Y (1999) VIP-, galanin-, and neuropeptide-Y-immunoreactive fibers in the chicken carotid bodies after various types of denervation. Cell Tissue Res 298:437–447

    Article  CAS  PubMed  Google Scholar 

  • Kim D-K, Oh EK, Summers BA, Prabhakar NR, Kumar GK (2001) Release of substance P by low oxygen in the rabbit carotid body: evidence for the involvement of calcium channels. Brain Res 892:359–369

    Article  CAS  PubMed  Google Scholar 

  • Kirby GC, McQueen DS (1986) Characterization of opioid receptors in the cat carotid body involved in chemosensory depression in vivo. Br J Pharmacol 88:889–898

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kobayashi S, Uchida T, Ohashi T, Fujita T, Nakao K, Yoshimasa T, Imura H, Mochizuki T, Yanaihara C, Yanaihara N, Verhofstad AAJ (1983) Immunocytochemical demonstration of the co-storage of noradrenaline with Met-enkephalin-Arg6-Phe7 and Met-enkephalin-Arg6-Gly7-Leu8 in the carotid body chief cells of the dog. Arch Histol Jpn 46:713–722

    Article  CAS  PubMed  Google Scholar 

  • Koelle GB (1950) The histochemical differentiation of types of cholinesterases and their localization in tissues of the cat. J Pharmac Exp Ther 100:158–179

    CAS  Google Scholar 

  • Koelle GB (1951) The elimination of enzymic diffusion artefacts in the histochemical localization of cholinesterases and a survey of their cellular distribution. J Pharmac Exp Ther 103:153–171

    CAS  Google Scholar 

  • Koerner P, Hesslinger C, Schaefermeyer A, Prinz C, Gratzl M (2004) Evidence for histamine as a transmitter in rat carotid body sensor cells. J Neurochem 91:493–500

    Article  CAS  PubMed  Google Scholar 

  • Kondo H, Yamamoto M (1988) Occurrence, ontogeny, ultrastructure and some plasticity of CGRP (calcitonin gene-related peptide)-immunoreactive nerves in the carotid body of rats. Brain Res 473:283–293

    Article  CAS  PubMed  Google Scholar 

  • Kondo H, Kuramoto H, Fujita T (1986) Neuropeptide tyrosine-like immunoreactive nerve fibers in the carotid body chemoreceptor of rats. Brain Res 372:353–356

    Article  CAS  PubMed  Google Scholar 

  • Kumar GK (1997) Peptidases of the peripheral chemoreceptors: biochemical, immunological, in vitro hydrolytic studies and electron microscopic analysis of neutral endopeptidase-like activity of the carotid body. Brain Res 748:39–50

    Article  CAS  PubMed  Google Scholar 

  • Kumar GK, Kou YR, Overholt JL, Prabhakar NR (2000) Involvement of substance P in neutral endopeptidase modulation of carotid body sensory responses to hypoxia. J Appl Physiol 88:195–202

    Article  CAS  PubMed  Google Scholar 

  • Kumar GK, Overholt JL, Prabhakar NR (2003) Multiple roles of neurotransmitters in the carotid body. In: Lahiri S, Semenza GL, Prabhakar NR (eds) Oxygen sensing: responses and adaptation to hypoxia, vol 175. Dekker, New York, pp 421–438

    Google Scholar 

  • Kummer W (1990) Three types of neurochemically defined autonomic fibres innervate the carotid baroreceptor and chemoreceptor regions in the guinea-pig. Anat Embryol 181:477–489

    Article  CAS  Google Scholar 

  • Kummer W, Habeck JO (1991) Substance P- and calcitonin gene-related peptide-like immunoreactivities in the human carotid body studied at light and electron microscopical level. Brain Res 554:286–292

    Article  CAS  PubMed  Google Scholar 

  • Kummer W, Habeck JO (1993) Light- and electronmicroscopical immunohistochemical investigation of the innervation of the human carotid body. In: Data PG, Acker H, Lahiri S (eds) Neurobiology and cell physiology of chemoreception, vol 337. Springer, Boston, pp 67–71

    Google Scholar 

  • Kummer W, Fischer A, Heym C (1989a) Ultrastructure of calcitonin gene-related peptide- and substance P-like immunoreactive nerve fibres in the carotid body and carotid sinus of the guinea pig. Histochemistry 92:433–439

    Article  CAS  PubMed  Google Scholar 

  • Kummer W, Gibbins IL, Heym C (1989b) Peptidergic innervation of arterial chemoreceptors. Arch Histol Cytol 52:361–364

    Article  PubMed  Google Scholar 

  • Kusakabe T, Anglade P, Tsuji S (1991) Localization of substance P, CGRP, VIP, neuropeptide Y, and somatostatin immunoreactive nerve fibers in the carotid labyrinths of some amphibian species. Histochemistry 96:255–260

    Article  CAS  PubMed  Google Scholar 

  • Kusakabe T, Kawakami T, Tanabe Y, Fujii S, Takenaka T (1994) Distribution of substance P-containing and catecholaminergic nerve fibers in the rabbit carotid body: an immunohistochemical study in combination with catecholamine fluorescent histochemistry. Arch Cytol Histol 57:193–199

    Article  CAS  Google Scholar 

  • Kusakabe T, Kawakami T, Takenaka T (1995) Peptidergic innervation in the amphibian carotid labyrinth. Histol Histopathol 10:185–202

    CAS  PubMed  Google Scholar 

  • Kusakabe T, Matsuda H, Harada H, Hayashida Y, Gono Y, Kawakami T, Takenaka T (1998a) Changes in the distribution of nitric oxide synthase immunoreactive nerve fibers in the chronically hypoxic rat carotid body. Brain Res 795:292–296

    Article  CAS  PubMed  Google Scholar 

  • Kusakabe T, Hayashida Y, Matsuda H, Gono Y, Powell FL, Ellisman MH, Kawakami T, Takenaka T (1998b) Hypoxic adaptation of the peptidergic innervation in the rat carotid body. Brain Res 806:165–174

    Article  CAS  PubMed  Google Scholar 

  • Kusakabe T, Matsuda H, Hirakawa H, Hayashida Y, Ichikawa T, Kawakami T, Takenaka T (2000) Calbindin D-28k immunoreactive nerve fibers in the carotid body of normoxic and chronically hypoxic rats. Histol Histopathol 15:1019–1025

    CAS  PubMed  Google Scholar 

  • Lahiri S, Mitchell CH, Reigada D, Roy A, Cherniack NS (2007) Purines, the carotid body and respiration. Respir Physiol Neurobiol 157:123–129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Laidler P, Kay JM (1975) The effect of chronic hypoxia on the number and nuclear diameter of type I cells in the carotid bodies of rats. Am J Pathol 79:311–318

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lam SY, Leung PS (2002) A locally generated angiotensin system in rat carotid body. Regul Pept 107:97–103

    Article  CAS  PubMed  Google Scholar 

  • Lam SY, Liu Y, Liong EC, Tipoe GL, Fung ML (2012) Upregulation of pituitary adenylate cyclase activating polypeptide and its receptor expression in the rat carotid body in chronic and intermittent hypoxia. Adv Exp Med Biol 758:301–306

    Article  CAS  PubMed  Google Scholar 

  • Lam SY, Liu Y, Ng KM, Liong EC, Tipoe GL, Leung PS, Fung ML (2014) Upregulation of a local renin-angiotensin system in the rat carotid body during chronic intermittent hypoxia. Exp Physiol 99:220–231

    Article  CAS  PubMed  Google Scholar 

  • Landgren S, Liljestrand G, Zotterman Y (1954) Impulse activity in the carotid sinus nerve following intracarotid injections of sodium-iodoacetate, histamine hydrochloride, lergitin, and some purine and barbituric acid derivatives. Acta Physiol Scand 30:149–160

    Article  CAS  PubMed  Google Scholar 

  • Lazarov N, Rozloznik M, Reindl S, Rey-Ares V, Dutschmann M, Gratzl M (2006) Expression of histamine receptors and effect of histamine in the rat carotid body chemoafferent pathway. Eur J Neurosci 24:3431–3444

    Article  PubMed  Google Scholar 

  • Lazarov N, Reindl S, Fischer F, Gratzl M (2009) Histaminergic and dopaminergic traits in the human carotid body. Respir Physiol Neurobiol 165:131–136

    Article  CAS  PubMed  Google Scholar 

  • Lazarov N, Atanasova D, Reindl S, Gratzl M (2011) Dopamine and histamine: two major transmitters in hypoxic chemosensitivity in the human carotid body. Clujul Med 2(Suppl 2):84–88

    Google Scholar 

  • Lazarov NE, Iliev ME, Atanasova DY (2013) Enzyme histochemical investigations of the mammalian carotid body. Scr Sci Med 45(Suppl 1):34–38

    Google Scholar 

  • Leonard EM, Nurse CA (2023) The carotid body “tripartite synapse”: role of gliotrasmission. In: Conde SV, Iturriaga R, del Rio R, Gauda E, Monteiro EC (eds) Arterial chemoreceptors, ISAC XXI 2022, vol 1427. Springer, Cham, pp 185–194

    Google Scholar 

  • Leonard EM, Salman S, Nurse CA (2018) Sensory processing and integration at the carotid body tripartite synapse: neurotransmitter functions and effects of chronic hypoxia. Front Physiol 9:225

    Article  PubMed  PubMed Central  Google Scholar 

  • Leung PS, Lam SY, Fung ML (2000) Chronic hypoxia upregulates the expression and function of AT1 receptor in rat carotid body. J Endocrinol 167:517–524

    Article  CAS  PubMed  Google Scholar 

  • Leung PS, Fung ML, Tam MS (2003) Renin-angiotensin system in the carotid body. Int J Biochem Cell Biol 35:847–854

    Article  CAS  PubMed  Google Scholar 

  • Li Q, Sun B, Wang X, Jin Z, Zhou Y, Dong L, Jiang LH, Rong W (2010) A crucial role for hydrogen sulfide in oxygen sensing via modulating large conductance calcium-activated potassium channels. Antioxid Redox Signal 12:1179–1189

    Article  CAS  PubMed  Google Scholar 

  • Li C, Huang L, Jia X, Zhao B, Chen L, Liu Y (2020) Functional glutamate transporters are expressed in the carotid chemoreceptor. Respir Res 21:208

    Article  PubMed  PubMed Central  Google Scholar 

  • Li C, Zhao B, Zhao C, Huang L, Liu Y (2021) Metabotropic glutamate receptors 1 regulates rat carotid body response to acute hypoxia via presynaptic mechanism. Front Neurosci 15:741214

    Article  PubMed  PubMed Central  Google Scholar 

  • Limberg JK, Johnson BD, Mozer MT, Holbein WW, Curry TB, Prabhakar NR, Joyner MJ (2020) Role of the carotid chemoreceptors in insulin-mediated sympathoexcitation in humans. Am J Physiol Regul Integr Comp Physiol 318:R173–R181

    Article  CAS  PubMed  Google Scholar 

  • Liu Y, Ji ES, Xiang S, Tamisier R, Tong J, Weiss JW (2009) Exposure to cyclic intermittent hypoxia increases expression of functional NMDA receptors in the rat carotid body. J Appl Physiol 106:259–267

    Article  CAS  PubMed  Google Scholar 

  • Liu Y, Li C, Jia X, Huang L, Weiss JW (2018) AMPA receptor-dependent glutamatergic signaling is present in the carotid chemoreceptor. Neuroscience 382:59–68

    Article  CAS  PubMed  Google Scholar 

  • López-Barneo J, Ortega-Sáenz P, González-Rodríguez P, Fernández-Agüera MC, Macías D, Pardal R, Gao L (2016) Oxygen sensing by arterial chemoreceptors: mechanisms and medical translation. Mol Aspects Med 47–48:90–108

    Article  PubMed  Google Scholar 

  • López-López JR, González C, Pérez-García MT (1997) Properties of ionic currents from isolated adult rat carotid body chemoreceptor cells: effect of hypoxia. J Physiol 499(Pt 2):429–441

    Article  PubMed  PubMed Central  Google Scholar 

  • Lundberg JM, Hökfelt T, Fahrenkrug J, Nilsson G, Terenius L (1979) Peptides in the cat carotid body (glomus caroticum): VIP-, enkephalin- and substance P-like immunoreactivity. Acta Physiol Scand 107:279–281

    Article  CAS  PubMed  Google Scholar 

  • Makarenko VV, Nanduri J, Raghuraman G, Fox AP, Gadalla MM, Kumar GK, Snyder SH, Prabhakar NR (2012) Endogenous H2S is required for hypoxic sensing by carotid body glomus cells. Am J Physiol Cell Physiol 303:C916–C923

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mazzatenta A, Marconi GD, Zara S, Cataldi A, Porzionato A, Di Giulio CD (2014) In the carotid body, galanin is a signal for neurogenesis in young, and for neurodegeneration in the old and in drug-addicted subjects. Front Physiol 5:427

    Article  PubMed  PubMed Central  Google Scholar 

  • McDonald DM, Mitchell RA (1975) The innervation of glomus cells, ganglion cells and blood vessels in the rat carotid body: a quantitative ultrastructural study. J Neurocytol 4:177–230

    Article  Google Scholar 

  • McQueen DS (1980) Effects of substance P on carotid chemoreceptor activity in the cat. J Physiol 302:31–47

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McQueen DS, Ribeiro JA (1981) Effect of adenosine on carotid chemoreceptor activity in the cat. Br J Pharmacol 74:129–136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McQueen DS, Ribeiro JA (1983) On the specificity and type of receptor involved in carotid body chemoreceptor activation by adenosine in the cat. Br J Pharmacol 80:347–354

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Messenger SA, Ciriello J (2013) Effects of intermittent hypoxia on signalling in the carotid body. Neuroscience 232:216–225

    Article  CAS  PubMed  Google Scholar 

  • Mir AK, Al-Neamy K, Pallot DJ, Nahorski SR (1982) Catecholamines in the carotid body of several mammalian species: effects of surgical and chemical sympathectomy. Brain Res 252:335–342

    Article  CAS  PubMed  Google Scholar 

  • Mir AK, Pallot DJ, Nahorski SR (1983) Biogenic amine-stimulated cyclic adenosine-3I,5I-monophosphate formation in the rat carotid body. J Neurochem 41:663–669

    Article  CAS  PubMed  Google Scholar 

  • Mokashi A, Li J, Roy A, Baby SM, Lahiri S (2003) ATP causes glomus cell [Ca2+]c increase without corresponding increases in CSN activity. Respir Physiol Neurobiol 138:1–18

    Article  CAS  PubMed  Google Scholar 

  • Monti-Bloch L, Eyzaguirre C (1985) Effects of methionine-enkephalin and substance P on the chemosensory discharge of the cat carotid body. Brain Res 338:297–307

    Article  CAS  PubMed  Google Scholar 

  • Moya EA, Alcayaga J, Iturriaga R (2012) NO modulation of carotid body chemoreception in health and disease. Respir Physiol Neurobiol 184:158–164

    Article  CAS  PubMed  Google Scholar 

  • Murali S, Nurse CA (2016) Purinergic signalling mediates bidirectional crosstalk between chemoreceptor type I and glial-like type II cells of the rat carotid body. J Physiol 594:391–406

    Article  CAS  PubMed  Google Scholar 

  • Nada O, Ulano Y (1972) Adenosine triphosphatase activity in the carotid body of the cat. a light and electron microscopic study. Z Zellforsch 130:455–462

    Article  CAS  PubMed  Google Scholar 

  • Nishi K, Iwasaki K, Kase Y (1979) Actions of piperidine and dimethylphenylpiperazinium (DMPP) on afferent discharges of the cat’s carotid body. Eur J Pharmacol 54:141–152

    Article  CAS  PubMed  Google Scholar 

  • Nurse CA (1987) Localization of acetylcholinesterase in dissociated cell cultures of the carotid body of the rat. Cell Tissue Res 250:21–27

    Article  CAS  PubMed  Google Scholar 

  • Nurse CA (2005) Neurotransmission and neuromodulation in the chemosensory carotid body. Auton Neurosci 120:1–9

    Article  CAS  PubMed  Google Scholar 

  • Nurse CA (2010) Neurotransmitter and neuromodulatory mechanisms at peripheral arterial chemoreceptors. Exp Physiol 95:657–667

    Article  CAS  PubMed  Google Scholar 

  • Nurse CA (2014) Synaptic and paracrine mechanisms at carotid body arterial chemoreceptors. J Physiol 592:3419–3426

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nurse CA, Piskuric NA (2013) Signal processing at mammalian carotid body chemoreceptors. Semin Cell Dev Biol 24:22–30

    Article  CAS  PubMed  Google Scholar 

  • Nurse CA, Zhang M (1999) Acetylcholine contributes to hypoxic chemotransmission in co-cultures of rat type 1 cells and petrosal neurons. Respir Physiol 115:189–199

    Article  CAS  PubMed  Google Scholar 

  • Ohtomo K, Fukuhara K, Yoshizaki K (2002) Immunohistochemical study of the carotid body during hibernation. Adv Exp Med Biol 475:815–821

    Article  Google Scholar 

  • Oomori Y, Ishikawa K, Satoh Y, Matsuda M, Ono K (1991) Neuropeptide-Y-immunoreactive chief cells in the carotid body of young rats. Acta Anat 140:120–123

    Article  CAS  PubMed  Google Scholar 

  • Oomori Y, Nakaya K, Tanaka H, Iuchi H, Ishikawa K, Satoh Y, Ono K (1994) Immunohistochemical and histochemical evidence for the presence of noradrenaline, serotonin and gamma-aminobutyric acid in chief cells of the mouse carotid body. Cell Tissue Res 278:249–254

    Article  CAS  PubMed  Google Scholar 

  • Oomori Y, Ishikawa K, Satoh Y, Ono K (1995) Electronmicroscopic study of gamma-aminobutyric acid immunoreactivity in the chief cells of the mouse carotid body. Acta Anat 154:143–146

    Article  CAS  PubMed  Google Scholar 

  • Ortega-Sáenz P, Pascual A, Gómez-Díaz R, López-Barneo J (2006) Acute oxygen sensing in heme oxygenase-2 null mice. J Gen Physiol 128:405–411

    Article  PubMed  PubMed Central  Google Scholar 

  • Otlyga D, Tsvetkova E, Junemann O, Saveliev S (2021) Immunohistochemical characteristics of the human carotid body in the antenatal and postnatal periods of development. Int J Mol Sci 22:8222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Overholt JL, Prabhakar NR (1999) Norepinephrine inhibits a toxin resistant Ca2+ current in carotid body glomus cells: evidence for a direct G protein mechanism. J Neurophysiol 81:225–233

    Article  CAS  PubMed  Google Scholar 

  • Overholt JL, Bright GR, Prabhakar NR (1996) Carbon monoxide and carotid body chemoreception. In: Zapata P, Eyzaguirre C, Torrance RW (eds) Frontiers in arterial chemoreception, vol 410. Springer, Boston, pp 341–344

    Google Scholar 

  • Paciga M, Vollmer C, Nurse C (1999) Role of ET-1 in hypoxia-induced mitosis of cultured rat carotid body chemoreceptors. NeuroReport 10:3739–3744

    Article  CAS  PubMed  Google Scholar 

  • Pardal R, Ortega-Sáenz P, Durán R, López-Barneo J (2007) Glia-like stem cells sustain physiologic neurogenesis in the adult mammalian carotid body. Cell 131:364–377

    Article  CAS  PubMed  Google Scholar 

  • Pearse AGE (1969) The cytochemisty and ultrastructure of polypeptide hormone-producing cells of the APUD series and the embryologic, physiologic and pathologic implications of the concept. J Histochem Cytochem 17:303–313

    Article  CAS  PubMed  Google Scholar 

  • Peng YJ, Nanduria J, Raghuraman G, Souvannakitti D, Gadalla MM, Kumar GK, Snyder SH, Prabhakar NR (2010) H2S mediates O2 sensing in the carotid body. Proc Natl Acad Sci USA 107:10719–10724

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Peng YJ, Raghuraman G, Khan SA, Kumar GK, Prabhakar NR (2011) Angiotensin II evokes sensory long-term facilitation of the carotid body via NADPH oxidase. J Appl Physiol 111:964–970

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Piskuric NA, Nurse CA (2013) Expanding role of ATP as a versatile messenger at carotid and aortic body chemoreceptors. J Physiol 591:415–422

    Google Scholar 

  • Pokorski M, Lahiri S (1981) Effects of naloxone on carotid body chemoreception and ventilation in the cat. J Appl Physiol 51:1533–1538

    Google Scholar 

  • Pokorski M, Ohtani S (1999) GABA immunoreactivity in chemoreceptor cells of the cat carotid body. Acta Histochem Cytochem 32:179–182

    Article  CAS  Google Scholar 

  • Porzionato A, Macchi V, Parenti A, De Caro R (2008) Trophic factors in the carotid body. Int Rev Cell Mol Biol 269:1–58

    Article  CAS  PubMed  Google Scholar 

  • Porzionato A, Macchi V, Barzon L, Masi G, Belloni A, Parenti A, Palù G, De Caro R (2010) Expression and distribution of galanin receptor subtypes in the rat carotid body. Mol Med Rep 3:37–41

    CAS  PubMed  Google Scholar 

  • Porzionato A, Rucinski M, Macchi V, Stecco C, Castagliuolo I, Malendowicz LK, De Caro R (2011) Expression of leptin and leptin receptor isoforms in the rat and human carotid body. Brain Res 1385:56–67

    Article  CAS  PubMed  Google Scholar 

  • Prabhakar NR (1998) Endogenous carbon monoxide in control of respiration. Respir Physiol 114:57–64

    Article  CAS  PubMed  Google Scholar 

  • Prabhakar NR (1999) NO and CO as second messengers in oxygen sensing in the carotid body. Respir Physiol 115:161–168

    Article  CAS  PubMed  Google Scholar 

  • Prabhakar NR (2006) O2 sensing at the mammalian carotid body: why multiple O2 sensors and multiple transmitters? Exp Physiol 91:17–23

    Article  CAS  PubMed  Google Scholar 

  • Prabhakar NR (2012) Carbon monoxide (CO) and hydrogen sulfide (H2S) in hypoxic sensing by the carotid body. Respir Physiol Neurobiol 184:165–169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prabhakar NR, Peers C (2014) Gasotransmitter regulation of ion channels: a key step in O2 sensing by the carotid body. Physiology (Bethesda) 29:49–57

    CAS  PubMed  Google Scholar 

  • Prabhakar NR, Semenza GL (2012) Gaseous messengers in oxygen sensing. J Mol Med (Berl) 90:265–272

    Article  CAS  PubMed  Google Scholar 

  • Prabhakar NR, Mitra J, Lagercrantz H, von Euler C, Cherniack NS (1987) Substance P and hypoxic excitation of the carotid body. In: Henry JL, Couture R, Cuello AC, Pelletier G, Quirion R, Regoli D (eds) Substance P and neurokinins. Springer, New York, pp 263–265

    Chapter  Google Scholar 

  • Prabhakar NR, Landis SC, Kumar GK, Mullikin-Kilpatrick D, Cherniack NS, Leeman S (1989) Substance P and neurokinin A in the cat carotid body: localization, exogenous effects and changes in content in response to arterial pO2. Brain Res 481:205–214

    Article  CAS  PubMed  Google Scholar 

  • Prabhakar NR, Cao H, Lowe JA 3rd, Snider RM (1993) Selective inhibition of the carotid body sensory response to hypoxia by the substance P receptor antagonist CP-96,345. Proc Natl Acad Sci USA 90:10041–10045

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prabhakar NR, Dinerman JL, Agani FH, Snyder SH (1995) Carbon monoxide: a role in carotid body chemoreception. Proc Natl Acad Sci USA 92:1994–1997

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prasad M, Fearon IM, Zhang M, Laing M, Vollmer C, Nurse CA (2001) Expression of P2X2 and P2X3 receptor subunits in rat carotid body afferent neurones: role in chemosensory signalling. J Physiol 537:667–677

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rey S, Iturriaga R (2004) Endothelins and nitric oxide: vasoactive modulators of carotid body chemoreception. Curr Neurovasc Res 1:465–473

    Article  CAS  PubMed  Google Scholar 

  • Ribeiro MJ, Sacramento JF, González C, Guarino MP, Monteiro EC, Conde SV (2013) Carotid body denervation prevents the development of insulin resistance and hypertension induced by hypercaloric diets. Diabetes 62:2905–2916

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ribeiro MJ, Lima PA, Obeso A, Particio C, Conde SV (2016) Insulin action at the rat carotid body is mediated through the activation of Kv1.3 channels. Proc Physiol Soc 37:PCB205

    Google Scholar 

  • Ribeiro MJ, Sacramento JF, Gallego-Martin T, Olea E, Melo BF, Guarino MP, Yubero S, Obeso A, Conde SV (2018) High fat diet blunts the effects of leptin on ventilation and on carotid body activity. J Physiol 596:3187–3199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roumy M, Armengaud C, Leitner LM (1990) Catecholamines in the carotid body. In: Eyzaguirre C, Fidone SJ, Fitzgerald RS, Lahiri S, McDonald DM (eds) Arterial chemoreception. Springer, New York, NY, pp 115–123

    Chapter  Google Scholar 

  • Schamel A, Verna A (1992) Norepinephrine-containing glomus cells in the rabbit carotid body. II. Immunocytochemical evidence of dopamine-beta-hydroxylase and norepinephrine. J Neurocytol 21:353–362

    Article  CAS  PubMed  Google Scholar 

  • Schultz HD (2011) Angiotensin and carotid body chemoreception in heart failure. Curr Opin Pharmacol 11:144–149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scraggs M, Smith P, Heath D (1992) Glomic cells and their peptides in the carotid body of the human fetus. Pediatr Pathol 12:823–834

    Article  CAS  PubMed  Google Scholar 

  • Shin M-K, Caballero-Eraso C, Mu YP, Gu C, Hyeung BH, Kim LJ, Liu X-R, Wu Z-J, Paudel O, Pichard LE, Shirahata M, Tang W-Y, Sham JSK, Polotsky VY (2019) Leptin induces hypertension acting on transient receptor potential melastatin 7 channel in the carotid body. Circ Res 125:989–1002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shirahata M, Ishizawa Y, Igarashi A, Fitzgerald RS (1996) Release of acetylcholine from cultured cat and pig glomus cells. Adv Exp Med Biol 410:233–237

    Article  CAS  PubMed  Google Scholar 

  • Shirahata M, Ishizawa Y, Rudisill M, Schofield B, Fitzgerald RS (1998) Presence of nicotinic acetylcholine receptors in cat carotid body afferent system. Brain Res 814:213–217

    Article  CAS  PubMed  Google Scholar 

  • Shirahata M, Hirasawa S, Okumura M, Mendoza JA, Okumura A, Balbir A, Fitzgerald RS (2004) Identification of M1 and M2 muscarinic acetylcholine receptors in the cat carotid body chemosensory system. Neuroscience 128:635–644

    Article  CAS  PubMed  Google Scholar 

  • Shirahata M, Balbir A, Otsubo T, Fitzgerald RS (2007) Role of acetylcholine in neurotransmission of the carotid body. Resp Physiol Neurobiol 157:93–105

    Article  CAS  Google Scholar 

  • Smith P, Gosney J, Heath D, Burnett H (1990) The occurrence and distribution of certain polypeptides within the human carotid body. Cell Tissue Res 261:565–571

    Article  CAS  PubMed  Google Scholar 

  • Snyder SH (1992) Nitric oxide: first in a new class of neurotrasnmitters. Science 257:494–496

    Article  CAS  PubMed  Google Scholar 

  • Spergel D, Lahiri S (1993) Differential modulation by extracellular ATP of carotid chemosensory response. J Appl Physiol 74:3052–3056

    Article  CAS  PubMed  Google Scholar 

  • Starlinger H (1982) ATPases of the cat carotid body and of neighbouring ganglia. Z Naturforsch 37:532–539

    Article  CAS  Google Scholar 

  • Summers BA, Overholt JL, Prabhakar NR (1999) Nitric oxide inhibits L-type Ca2+ current in glomus cells of the rabbit carotid body via a cGMP-independent mechanism. J Neurophysiol 81:1449–1457

    Article  CAS  PubMed  Google Scholar 

  • Tanaka K, Chiba T (1994) Nitric oxide synthase containing neurons in the carotid body and sinus of the guinea pig. Microsc Res Tech 29:90–93

    Article  CAS  PubMed  Google Scholar 

  • Tankersley CG (2003) Genetic aspects of breathing: on interactions between hypercapnia and hypoxia. Respir Physiol Neurobiol 135:167–178

    Article  CAS  PubMed  Google Scholar 

  • Telezhkin V, Brazier SP, Cayzac SH, Wilkinson WJ, Riccardi D, Kemp PJ (2010) Mechanism of inhibition by hydrogen sulfide of native and recombinant BKCa channels. Respir Physiol Neurobiol 172:169–178

    Article  CAS  PubMed  Google Scholar 

  • Thybusch D (1968) Monaminoxidasenachweis im Glomus caroticum. Acta Histochem 30:192–194

    CAS  PubMed  Google Scholar 

  • Torrealba F (1990) Immunocytochemistry of neuroactive substances in visceral receptors: glutamate and CGRP. Arch Biol Med Exp 23:R222

    Google Scholar 

  • Torrealba F, Correa R (1995) Ultrastructure of calcitonin gene-related peptide-immunoreactive, unmyelinated afferents to the cat carotid body: a case of volume transmission. Neuroscience 64:777–785

    Article  CAS  PubMed  Google Scholar 

  • Torrealba F, Bustos G, Montero VM (1996) Glutamate in the glomus cells of the cat carotid body: immunocytochemistry and in vitro release. Neurochem Int 28:625–631

    Article  CAS  PubMed  Google Scholar 

  • Varas R, Alcayaga J, Iturriaga R (2003) ACh and ATP mediate excitatory transmission in identified cat carotid body chemoreceptor units in vitro. Brain Res 988:154–163

    Article  CAS  PubMed  Google Scholar 

  • Vardhan A, Kachroo A, Sapru HN (1993) Excitatory amino acid receptors in commissural nucleus of the NTS mediate carotid chemoreceptor responses. Am J Physiol 264:R41–R50

    CAS  PubMed  Google Scholar 

  • Varndell IM, Tapia FJ, De Mey J, Rush RA, Bloom SR, Polak JM (1982) Electron immunocytochemical localization of enkephalin-like material in catecholamine-containing cells of the carotid body, the adrenal medulla, and in pheochromocytomas of man and other mammals. J Histochem Cytochem 30:682–690

    Article  CAS  PubMed  Google Scholar 

  • Verna A, Schamel A, Pequignot JM (1993) Noradrenergic glomus cells in the carotid body: an autoradiographic and immunocytochemical study in the rabbit and rat. Adv Exp Med Biol 337:93–100

    Article  CAS  PubMed  Google Scholar 

  • Verna A, Schamel A, Le Moine C, Bloch B (1995) Localization of dopamine D2 receptor mRNA in glomus cells of the rabbit carotid body by in situ hybridization. J Neurocytol 24:265–270

    Article  CAS  PubMed  Google Scholar 

  • Vicario I, Rigual R, Obeso A, González C (2000) Characterization of the synthesis and release of catecholamine in the rat carotid body in vitro. Am J Physiol Cell Physiol 278:490–499

    Article  Google Scholar 

  • Wang ZZ, Stensaas LJ, Dinger B, Fidone SJ (1989) Immunocytochemical localization of choline acetyltransferase in the carotid body of the cat and rabbit. Brain Res 498:131–134

    Article  CAS  PubMed  Google Scholar 

  • Wang ZZ, Stensaas LJ, Dinger B, Fidone SJ (1991) The co-existence of tyrosine hydroxylase and dopamine β-hydroxylase immunoreactivity in glomus cells of the cat carotid body. J Auton Nerv Syst 32:259–264

    Article  CAS  PubMed  Google Scholar 

  • Wang ZZ, Stensaas LJ, Dinger B, Fidone SJ (1992) The co-existence of biogenic amines and neuropeptides in the type I cells of the cat carotid body. Neuroscience 47:473–480

    Article  CAS  PubMed  Google Scholar 

  • Wang ZZ, Bredt DS, Fidone SJ, Stensaas LJ (1993) Neurons synthesizing nitric oxide innervate the mammalian carotid body. J Comp Neurol 336:419–432

    Article  CAS  PubMed  Google Scholar 

  • Wang ZZ, Stensaas LJ, Bredt DS, Dinger B, Fidone SJ (1994) Localization and actions of nitric oxide in the cat carotid body. Neuroscience 60:275–286

    Article  CAS  PubMed  Google Scholar 

  • Wang ZZ, Dinger BG, Stensaas LJ, Fidone SJ (1995a) The role of nitric oxide in carotid chemoreception. Biol Signals 4:109–116

    Article  CAS  PubMed  Google Scholar 

  • Wang ZZ, Stensaas LJ, Dinger BG, Fidone SJ (1995b) Nitric oxide mediates chemoreceptor inhibition in the cat carotid body. Neuroscience 65:217–229

    Article  CAS  PubMed  Google Scholar 

  • Wang Z-Y, Keith IM, Beckman MJ, Brownfield MS, Vidruk EH, Bisgard GE (2000) 5-HT5a receptors in the carotid body chemoreception pathway of rat. Neurosci Lett 278:9–12

    Article  CAS  PubMed  Google Scholar 

  • Wharton J, Polak JM, Pearse AGE, McGregor GP, Bryant MG, Bloom SR, Emson PC, Bisgard GE, Will JA (1980) Enkephalin-, VIP- and substance P-like immunoreactivity in the carotid body. Nature (London) 284:269–271

    Article  CAS  PubMed  Google Scholar 

  • Woods RI (1967) Distribution of cytochrome oxidase, monoamine oxidase and carbonic anhydrase in the carotid body of the rabbit. Nature 213:1240

    Article  CAS  Google Scholar 

  • Woods RI (1975) Penetration of horseradish peroxidase between all elements of the carotid body. In: Purves MJ (ed) The peripheral arterial chemoreceptors. Cambridge Univ Press, London, pp 195–205

    Google Scholar 

  • Xu J, Tse FW, Tse A (2003) ATP triggers intracellular Ca2+ release in type II cells of the rat carotid body. J Physiol 549:739–747

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu F, Tse FW, Tse A (2008) Stimulatory actions of pituitary adenylate cyclase-activating polypeptide (PACAP) in rat carotid glomus cells. Adv Exp Med Biol 605:69–74

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto M, Kondo H, Nagatu I (1989) Immunohistochemical demonstration of tyrosine hydroxylase, serotonin and neuropeptide tyrosine in the epithelioid cells within arterial walls and carotid bodies of chicks. J Anat 167:137–146

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yokoyama T, Misuzu YY, Yamamoto Y (2013) Immunohistochemical localization of tryptophan hydroxylase and serotonin transporter in the carotid body of the rat. Histochem Cell Biol 140:147–155

    Article  CAS  PubMed  Google Scholar 

  • Yokoyama T, Nakamuta N, Kusakabe T, Yamamoto Y (2014) Vesicular glutamate transporter 2-immunoreactive afferent nerve terminals in the carotid body of the rat. Cell Tissue Res 358:271–275

    Article  CAS  PubMed  Google Scholar 

  • Zapata P (1977) Modulatory role of dopamine on arterial chemoreceptors. Adv Biochem Psychopharmacol 16:291–298

    CAS  PubMed  Google Scholar 

  • Zapata P (2007) Is ATP a suitable co-transmitter in carotid body arterial chemoreceptors? Respir Physiol Neurobiol 157:106–115

    Google Scholar 

  • Zhang M, Nurse CA (2000) Does endogenous 5-HT mediate spontaneous rhythmic activity in chemoreceptor clusters of rat carotid body? Brain Res 872:199–203

    Google Scholar 

  • Zhang M, Nurse CA (2004) CO2/pH chemosensory signaling in co-cultures of rat carotid body receptors and petrosal neurons: role of ATP and ACh. J Neurophysiol 92:3433–3445

    Article  CAS  PubMed  Google Scholar 

  • Zhang M, Zhong H, Vollmer C, Nurse CA (2000) Co-release of ATP and ACh mediates hypoxic signalling at rat carotid body chemoreceptors. J Physiol 525:143–158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang M, Fearon IM, Zhong H, Nurse CA (2003) Presynaptic modulation of rat arterial chemoreceptor function by 5-HT: role of K+ channel inhibition via protein kinase C. J Physiol (Lond) 551:825–842

    Article  CAS  PubMed  Google Scholar 

  • Zhang M, Clarke K, Zhong H, Vollmer C, Nurse CA (2009) Postsynaptic action of GABA in modulating sensory transmission in co-cultures of rat carotid body via GABAA receptors. J Physiol 587:329–344

    Article  CAS  PubMed  Google Scholar 

  • Zhang M, Piskuric NA, Vollmer C, Nurse CA (2012) P2Y2 receptor activation opens pannexin-1 channels in rat carotid body type II cells: potential role in amplifying the neurotransmitter ATP. J Physiol 590:4335–4350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao C, Li C, Zhao B, Liu Y (2022) Expression of group II and III mGluRs in the carotid body and its role in the carotid chemoreceptor response to acute hypoxia. Front Physiol 13:1008073

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nikolai E. Lazarov .

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Lazarov, N.E., Atanasova, D.Y. (2023). Neurochemical Anatomy of the Mammalian Carotid Body. In: Morphofunctional and Neurochemical Aspects of the Mammalian Carotid Body. Advances in Anatomy, Embryology and Cell Biology, vol 237. Springer, Cham. https://doi.org/10.1007/978-3-031-44757-0_6

Download citation

Publish with us

Policies and ethics