Advertisement

Histochemistry and Cell Biology

, Volume 151, Issue 2, pp 161–173 | Cite as

Distribution and morphology of baroreceptors in the rat carotid sinus as revealed by immunohistochemistry for P2X3 purinoceptors

  • Takuya Yokoyama
  • Kazuya Settai
  • Nobuaki Nakamuta
  • Yoshio YamamotoEmail author
Original Paper
  • 213 Downloads

Abstract

The morphological characteristics of baroreceptors in the rat carotid sinus were reevaluated by whole-mount preparations with immunohistochemistry for P2X3 purinoceptors using confocal scanning laser microscopy. Immunoreactive nerve endings for P2X3 were distributed in the internal carotid artery proximal to the carotid bifurcation, particularly in the region opposite the carotid body. Some pre-terminal axons in nerve endings were ensheathed by myelin sheaths immunoreactive for myelin basic protein. Pre-terminal axons ramified into several branches that extended two-dimensionally in every direction. The axon terminals of P2X3-immunoreactive nerve endings were flat and leaf-like in shape, and extended hederiform- or knob-like protrusions in the adventitial layer. Some axons and axon terminals with P2X3 immunoreactivity were also immunoreactive for P2X2, and axon terminals were closely surrounded by terminal Schwann cells with S100 or S100B immunoreactivity. These results revealed the detailed morphology of P2X3-immunoreactive nerve endings and suggested that these endings respond to a mechanical deformation of the carotid sinus wall with their flat leaf-like terminals.

Keywords

Carotid sinus Sensory nerve endings P2X purinoreceptor Immunohistochemistry 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

Supplementary material

418_2018_1734_MOESM1_ESM.docx (201 kb)
Supplementary material 1 (DOCX 201 KB)

References

  1. Baluk P, Gabella G (1991) Afferent nerve endings in the tracheal muscle of guinea-pigs and rats. Anat Embryol (Berl) 183:81–87CrossRefGoogle Scholar
  2. Besalduch N, Tomàs M, Santafé MM, Garcia N, Tomàs J, Lanuza MA (2010) Synaptic activity-related classical protein kinase C isoform localization in the adult rat neuromuscular synapse. J Comp Neurol 518:211–228CrossRefGoogle Scholar
  3. Böck P, Gorgas K (1976) Fine structure of baroreceptor terminals in the carotid sinus of guinea pigs and mice. Cell Tissue Res 170:95–112CrossRefGoogle Scholar
  4. Bronk DW, Stella G (1932) Afferent impulses in the carotid sinus nerve. J Cell Comp Physiol 1:113–130CrossRefGoogle Scholar
  5. Brouns I, Pintelon I, De Proost I, Alewaters R, Timmermans JP, Adriaensen D (2006) Neurochemical characterisation of sensory receptors in airway smooth muscle: comparison with pulmonary neuroepithelial bodies. Histochem Cell Biol 125:351–367CrossRefGoogle Scholar
  6. Brown AM, Saum WR, Yasui S (1978) Baroreceptor dynamics and their relationship to afferent fiber type and hypertension. Circ Res 42:694–702CrossRefGoogle Scholar
  7. Chaumont S, Compan V, Toulme E, Richler E, Housley GD, Rassendren F, Khakh BS (2008) Regulation of P2X2 receptors by the neuronal calcium sensor VILIP1. Sci Signal 1:ra8CrossRefGoogle Scholar
  8. Cho T, Chaban VV (2012) Interaction between P2X3 and oestrogen receptor (ER)α/ERβ in ATP-mediated calcium signalling in mice sensory neurones. J Neuroendocrinol 24:789–797CrossRefGoogle Scholar
  9. Coleridge HM, Coleridge JC, Schultz HD (1987) Characteristics of C fibre baroreceptors in the carotid sinus of dogs. J Physiol 394:291–313CrossRefGoogle Scholar
  10. Cotrina ML, Lin JH, Nedergaard M (1998) Cytoskeletal assembly and ATP release regulate astrocytic calcium signaling. J Neurosci 18:8794–8804CrossRefGoogle Scholar
  11. De Castro F (2009) Towards the sensory nature of the carotid body: Hering, de Castro and Heymans. Front Neuroanat 3:23CrossRefGoogle Scholar
  12. Drummond HA, Price MP, Welsh MJ, Abboud FM (1998) A molecular component of the arterial baroreceptor mechanotransducer. Neuron 21:1435–1441CrossRefGoogle Scholar
  13. Dunn PM, Zhong Y, Burnstock G (2001) P2X receptors in peripheral neurons. Prog Neurobiol 65:107–134CrossRefGoogle Scholar
  14. Enomoto K, Furuya K, Yamagishi S, Oka T, Maeno T (1994) The increase in the intracellular Ca2+ concentration induced by mechanical stimulation is propagated via release of pyrophosphorylated nucleotides in mammary epithelial cells. Pflugers Arch 427:533–542CrossRefGoogle Scholar
  15. Farkas D, Kraskauskas D, Drake JI, Alhussaini AA, Kraskauskiene V, Bogaard HJ, Cool CD, Voelkel NF, Farkas L (2014) CXCR4 inhibition ameliorates severe obliterative pulmonary hypertension and accumulation of C-kit+ cells in rats. PLoS One 9:e89810CrossRefGoogle Scholar
  16. Fidone SJ, Sato A (1969) A study of chemoreceptor and baroreceptor A and C-fibres in the cat carotid nerve. J Physiol 205:527–548CrossRefGoogle Scholar
  17. Fu K, Corbley MJ, Sun L et al (2008) SM16, an orally active TGF-beta type I receptor inhibitor prevents myofibroblast induction and vascular fibrosis in the rat carotid injury model. Arterioscler Thromb Vasc Biol 28:665–671CrossRefGoogle Scholar
  18. Hagemann TL, Connor JX, Messing A (2006) Alexander disease-associated glial fibrillary acidic protein mutations in mice induce Rosenthal fiber formation and a white matter stress response. J Neurosci 26:11162–11173CrossRefGoogle Scholar
  19. Hansen JT (1987) Morphology of the carotid sinus wall in normotensive and spontaneously hypertensive rats. Anat Rec 218:426–433CrossRefGoogle Scholar
  20. Hemmings-Mieszczak M, Dorn G, Natt FJ, Hall J, Wishart WL (2003) Independent combinatorial effect of antisense oligonucleotides and RNAi-mediated specific inhibition of the recombinant rat P2X3 receptor. Nucleic Acids Res 31:2117–2126CrossRefGoogle Scholar
  21. Henriksson J, Tjälve H (2000) Manganese taken up into the CNS via the olfactory pathway in rats affects astrocytes. Toxicol Sci 55:392–398CrossRefGoogle Scholar
  22. Hering HE (1924) Der sinus caroticus an der ursprungsstelle der carotis interna als ausgangsort eines hemmenden herzreflexes und depressorischen gefässreflexes. Munch Med Wochenschr 71:701–705Google Scholar
  23. Huang LC, Greenwood D, Thorne PR, Housley GD (2005) Developmental regulation of neuron-specific P2X3 receptor expression in the rat cochlea. J Comp Neurol 484:133–143CrossRefGoogle Scholar
  24. Ichikawa H, Sugimoto T (2004) The co-expression of P2X3 receptor with VR1 and VRL-1 in the rat trigeminal ganglion. Brain Res 998:130–135CrossRefGoogle Scholar
  25. Ilg EC, Schäfer BW, Heizmann CW (1996) Expression pattern of S100 calcium-binding proteins in human tumors. Int J Cancer 68:325–332CrossRefGoogle Scholar
  26. Ishida Y, Ugawa S, Ueda T, Yamada T, Shibata Y, Hondoh A, Inoue K, Yu Y, Shimada S (2009) P2X2- and P2X3-positive fibers in fungiform papillae originate from the chorda tympani but not the trigeminal nerve in rats and mice. J Comp Neurol 514:131–144CrossRefGoogle Scholar
  27. Katayama PL, Castania JA, Dias DP, Patel KP, Fazan R Jr, Salgado HC (2015) Role of chemoreceptor activation in hemodynamic responses to electrical stimulation of the carotid sinus in conscious rats. Hypertension 66:598–603CrossRefGoogle Scholar
  28. Kirchheim HR (1976) Systemic arterial baroreceptor reflexes. Physiol Rev 56:100–177CrossRefGoogle Scholar
  29. Knoche H, Addicks K (1976) Electron microscopic studies of the pressoreceptor fields of the carotid sinus of the dog. Cell Tissue Res 173:77–94CrossRefGoogle Scholar
  30. Krauhs JM (1979) Structure of rat aortic baroreceptors and their relationship to connective tissue. J Neurocytol 8:401–414CrossRefGoogle Scholar
  31. Lai PC, Huang YT, Wu CC, Lai CJ, Wang PJ, Chiu TH (2011) Ceftriaxone attenuates hypoxic-ischemic brain injury in neonatal rats. J Biomed Sci 18:69CrossRefGoogle Scholar
  32. Lang H, Li M, Kilpatrick LA, Zhu J, Samuvel DJ, Krug EL, Goddard JC (2011) Sox2 up-regulation and glial cell proliferation following degeneration of spiral ganglion neurons in the adult mouse inner ear. J Assoc Res Otolaryngol 12:151–171CrossRefGoogle Scholar
  33. Lau OC, Shen B, Wong CO, Tjong YW, Lo CY, Wang HC, Huang Y, Yung WH, Chen YC, Fung ML, Rudd JA, Yao X (2016) TRPC5 channels participate in pressure-sensing in aortic baroreceptors. Nat Commun 7:11947CrossRefGoogle Scholar
  34. Lazarowski ER, Boucher RC, Harden TK (2003) Mechanisms of release of nucleotides and integration of their action as P2X- and P2Y-receptor activating molecules. Mol Pharmacol 64:785–795CrossRefGoogle Scholar
  35. Liao WC, Wang YJ, Huang MC, Tseng GF (2013) Methylcobalamin facilitates collateral sprouting of donor axons and innervation of recipient muscle in end-to-side neurorrhaphy in rats. PLoS One 8:e76302CrossRefGoogle Scholar
  36. Lu Y, Ma X, Sabharwal R, Snitsarev V, Morgan D, Rahmouni K, Drummond HA, Whiteis CA, Costa V, Price M, Benson C, Welsh MJ, Chapleau MW, Abboud FM (2009) The ion channel ASIC2 is required for baroreceptor and autonomic control of the circulation. Neuron 64:885–897CrossRefGoogle Scholar
  37. Maeda T, Ochi K, Nakakura-Ohshima K, Youn SH, Wakisaka S (1999) The Ruffini ending as the primary mechanoreceptor in the periodontal ligament: its morphology, cytochemical features, regeneration, and development. Crit Rev Oral Biol Med 10:307–327CrossRefGoogle Scholar
  38. McDonald DM (1983) Morphology of the rat carotid sinus nerve. I. Course, connections, dimensions and ultrastructure. J Neurocytol 12:345–372CrossRefGoogle Scholar
  39. Miura M, Reis DJ (1972) The role of the solitary and paramedian reticular nuclei in mediating cardiovascular reflex responses from carotid baro- and chemoreceptors. J Physiol 223:525–548CrossRefGoogle Scholar
  40. Muhanna N, Horani A, Doron S, Safadi R (2007) Lymphocyte-hepatic stellate cell proximity suggests a direct interaction. Clin Exp Immunol 148:338–347CrossRefGoogle Scholar
  41. Nakakura-Ohshima K, Maeda T, Ohshima H, Noda T, Takano Y (1995) Postnatal development of periodontal Ruffini endings in rat incisors: an immunoelectron microscopic study using protein gene product 9.5 (PGP 9.5) antibody. J Comp Neurol 362:551–564CrossRefGoogle Scholar
  42. Pintelon I, Brouns I, De Proost I, Van Meir F, Timmermans JP, Adriaensen D (2007) Sensory receptors in the visceral pleura: neurochemical coding and live staining in whole mounts. Am J Respir Cell Mol Biol 36:541–551CrossRefGoogle Scholar
  43. Piskuric NA, Vollmer C, Nurse CA (2011) Confocal immunofluorescence study of rat aortic body chemoreceptors and associated neurons in situ and in vitro. J Comp Neurol 519:856–873CrossRefGoogle Scholar
  44. 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 537:667–677CrossRefGoogle Scholar
  45. Rees PM (1967) Observations on the fine structure and distribution of presumptive baroreceptor nerves at the carotid sinus. J Comp Neurol 131:517–548CrossRefGoogle Scholar
  46. Rogers RF, Paton JF, Schwaber JS (1993) NTS neuronal responses to arterial pressure and pressure changes in the rat. Am J Physiol 265:R1355–R1368CrossRefGoogle Scholar
  47. Schoultz TW, Swett JE (1974) Ultrastructural organization of the sensory fibers innervating the Golgi tendon organ. Anat Rec 179:147–162CrossRefGoogle Scholar
  48. Seagard JL, van Brederode JF, Dean C, Hopp FA, Gallenberg LA, Kampine JP (1990) Firing characteristics of single-fiber carotid sinus baroreceptors. Circ Res 66:1499–1509CrossRefGoogle Scholar
  49. Seagard JL, Hopp FA, Drummond HA, Van Wynsberghe DM (1993) Selective contribution of two types of carotid sinus baroreceptors to the control of blood pressure. Circ Res 72:1011–1022CrossRefGoogle Scholar
  50. Soda Y, Yamamoto Y (2012) Morphology and chemical characteristics of subepithelial laminar nerve endings in the rat epiglottic mucosa. Histochem Cell Biol 138:25–39CrossRefGoogle Scholar
  51. Song X, Gao X, Guo D, Yu Q, Guo W, He C, Burnstock G, Xiang Z (2012) Expression of P2X2 and P2X3 receptors in the rat carotid sinus, aortic arch, vena cava, and heart, as well as petrosal and nodose ganglia. Purinergic Signal 8:15–22CrossRefGoogle Scholar
  52. Suzuki M, Ebara S, Koike T, Tonomura S, Kumamoto K (2012) How many hair follicles are innervated by one afferent axon? A confocal microscopic analysis of palisade endings in the auricular skin of thy1-YFP transgenic mouse. Proc Jpn Acad Ser B Phys Biol Sci 88:583–595CrossRefGoogle Scholar
  53. Takahashi N, Nakamura N, Yamamoto Y (2016) Morphology of P2X3-immunoreactive nerve endings in the rat laryngeal mucosa. Histochem Cell Biol 145:131–146CrossRefGoogle Scholar
  54. Takahashi-Iwanaga H (2000) Three-dimensional microanatomy of longitudinal lanceolate endings in rat vibrissae. J Comp Neurol 426:259–269CrossRefGoogle Scholar
  55. Takahashi-Iwanaga H, Habara Y (2002) Adenosine 5′-triphosphate-evoked calcium responses in terminal Schwann cells of lanceolate sensory endings isolated from rat vibrissae. Neurosci Lett 324:137–140CrossRefGoogle Scholar
  56. Takahashi-Iwanaga H, Maeda T, Abe K (1997) Scanning and transmission electron microscopy of Ruffini endings in the periodontal ligament of rat incisors. J Comp Neurol 389:177–184CrossRefGoogle Scholar
  57. Takahashi-Iwanaga H, Nio-Kobayashi J, Habara Y, Furuya K (2008) A dual system of intercellular calcium signaling in glial nets associated with lanceolate sensory endings in rat vibrissae. J Comp Neurol 510:68–78CrossRefGoogle Scholar
  58. Vulchanova L, Riedl MS, Shuster SJ, Buell G, Surprenant A, North RA, Elde R (1997) Immunohistochemical study of the P2X2 and P2X3 receptor subunits in rat and monkey sensory neurons and their central terminals. Neuropharmacology 36:1229–1242CrossRefGoogle Scholar
  59. Wang ZJ, Neuhuber WL (2003) Intraganglionic laminar endings in the rat esophagus contain purinergic P2X2 and P2X3 receptor immunoreactivity. Anat Embryol (Berl) 207:363–371CrossRefGoogle Scholar
  60. Yamamoto Y, Nakamuta N (2018) Morphology of P2X3-immunoreactive nerve endings in the rat tracheal mucosa. J Comp Neurol 526:550–566CrossRefGoogle Scholar
  61. Yates RD, Chen I (1980) An electron microscopic study of the baroreceptors in the internal carotid artery of the spontaneously hypertensive rat. Cell Tissue Res 205:473–483CrossRefGoogle Scholar
  62. Yokoyama T, Saino T, Nakamuta N, Kusakabe T, Yamamoto Y (2016) Three-dimensional architectures of P2X2-/P2X3-immunoreactive afferent nerve terminals in the rat carotid body as revealed by confocal laser scanning microscopy. Histochem Cell Biol 146:479–488CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Anatomy (Cell Biology)Iwate Medical UniversityYahabaJapan
  2. 2.Laboratory of Veterinary Anatomy and Cell Biology, Faculty of AgricultureIwate UniversityMoriokaJapan

Personalised recommendations