Abstract
The expression of the P2X3 nucleotide receptor in embryonic day 14–18, postnatal day 1–14 and adult mouse sensory ganglia was examined using immunohistochemistry. Nearly all sensory neurons in dorsal root ganglia, trigeminal ganglia and nodose ganglia in embryos at embryonic day 14 expressed P2X3 receptors, but after birth there was a gradual decline to about 50% of neurons showing positive immunostaining for P2X3. In embryos there were only small neurons, while from postnatal day 7 both large and small neurons were present. Isolectin B4 (IB4)-positive neurons in dorsal, trigeminal and nodose ganglia did not appear until birth, but the numbers increased to about 50% by postnatal day 14 when a high proportion of IB4-positive neurons were also positively labelled for the P2X3 receptor. About 10% of neurons in dorsal, trigeminal and nodose ganglia were positive for calcitonin gene-related peptide in embryos, nearly all of which stained for P2X3 receptors. This increased postnatally to about 35–40% in adults, although only a few colocalised with P2X3 receptors. Neurofilament 200 was expressed in about 50% of neurons in trigeminal ganglia in the embryo, and this level persisted postnatally. All neurofilament 200-positive neurons stained for P2X3 in embryonic dorsal root ganglia, trigeminal ganglia and nodose ganglia, but by adulthood this was significantly reduced. The neurons that were positive for calbindin in embryonic dorsal, trigeminal and nodose ganglia showed colocalisation with P2X3 receptors, but few showed colocalisation postnatally.
Similar content being viewed by others
References
Alavi AM, Dubyak GR, Burnstock G (2001) Immunohistochemical evidence for ATP receptors in human dental pulp. J Dental Res 80:476–483
Alvarez FJ, Morris HR, Priestely JC (1991) Sub-populations of smaller diameter trigeminal primary afferent neurons defined by expression of calcitonin gene-related peptide and the cell surface oligosaccharide recognized by monoclonal antibody LA4. J Neurocytol 20:716–731
Andressen C, Blumcke I, Celio MR (1993) Calcium-binding proteins: selective markers of nerve cells. Cell Tissue Res 271:181–208
Averill S, McMahon SB, Clary DO, Reichardt LF, Priestley JV (1995) Immunocytochemical localization of trkA receptors in chemically identified subgroups of adult rat sensory neurons. Eur J Neurosci 7:1484–1494
Barden JA, Bennett MR (2000) Distribution of P2X purinoceptor clusters on individual rat dorsal root ganglion cells. Neurosci Lett 287:183–186
Bo X, Alavi A, Xiang Z, Oglesby I, Ford A, Burnstock G (1999) Localization of ATP-gated P2X2 and P2X3 receptor immunoreactive nerves in rat taste buds. Neuroreport 10:1107–1111
Boldogkö IZ, Schütz B, Sallach J, Zimmer A (2002) P2X3 receptor expression at early stage of mouse embryogenesis. Mech Dev 118:255–260
Bradbury EJ, Burnstock G, McMahon SB (1998) The expression of P2X3 purinoceptors in sensory neurons: effects of axotomy and glial-derived neurotrophic factor. Mol Cell Neurosci 12:256–268
Burnstock G (1996) Purinoceptors: ontogeny and phylogeny. Drug Dev Res 39:204–242
Burnstock G (2001) Purinergic signalling in development. In: Abbracchio MP, Williams M (eds) Handbook of experimental pharmacology, vol 151/I. Purinergic and pyrimidinergic signalling. I. Molecular, nervous and urogenitary system function. Springer, Berlin Heidelberg New York, pp 89–127
Carr PA, Yamamoto T, Karmy G, Baimbridge KG, Nagy JI (1989) Parvalbumin is highly colocalized with calbindin D28 k and rarely with calcitonin gene-related peptide in dorsal root ganglia neurons of rat. Brain Res 497:163–170
Caterina MJ, Schumacher MA, Tominage M, Rosen TA, Levine JD, Julius D (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389:816–824
Chen CC, Akopian AN, Sivilotti L, Colquhoun D, Burnstock G, Wood JN (1995) A P2X receptor expressed by a subset of sensory neurons. Nature 377:428–430
Cheung K, Burnstock G (2002) Localization of P2X3 receptors and coexpression with P2X2 receptors during rat embryonic neurogenesis. J Comp Neurol 443:368–382
Cockayne DA, Hamilton SG, Zhu Q-M, Dunn PM, Zhong Y, Novakovic S, Malmberg AB, Cain G, Berson A, Kassotakis L, Lachnit WG, Burnstock G, McMahon SB, Ford APDW (2000) Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice. Nature 407:1011–1015
Cook SP, Vulchanova L, Hargreaves KM, Elde R, McCleskey EW (1997) Distinct ATP receptors on pain-sensing and stretch-sensing neurons. Nature 387:505–508
Dodd J, Jessell TM (1985) Lactoseries carbohydrates specify subsets of dorsal root ganglion neurons projecting to the superficial dorsal horn of rat spinal cord. J Neurosci 5:3278–3294
Dunn PM, Liu M, Zhong Y, King BF, Burnstock G (2000) Diinosine pentaphosphate: an antagonist which discriminates between recombinant P2X(3) and P2X(2/3) receptors and between two P2X receptors in rat sensory neurons. Br J Pharmacol 130:1378–1384
Dunn PM, Zhong Y, Burnstock G (2001) P2X receptors in peripheral neurons. Prog Neurobiol 65:107–134
Fried K, Arvidsson J, Robertson B, Brodin E, Theodorsson E (1989) Combined retrograde tracing and enzyme/immunohistochemistry of trigeminal ganglion cell bodies innervating tooth pulps in the rat. Neuroscience 33:101–109
Gerke MB, Plenderleith MB (2001) Binding sites for the plant lectin Bandeiraea simplicifolia I-isolectin B(4) are expressed by nociceptive primary sensory neurons. Brain Res 911:101–104
Grkovic I, Anderson CR (1997) Calbindin D28k-immunoreactivity identifies distinct subpopulations of sympathetic pre- and postganglionic neurons in the rat. J Comp Neurol 386:245–259
Guo A, Vulchanova L, Wang J, Li X, Elde R (1999) Immunocytochemical localization of the vanilloid receptor 1 (VR1): relationship to neuropeptides, the P2X3 purinoceptor and IB4 binding sites. Eur J Neurosci 11:946–958
Honda CN (1995) Differential distribution of calbindin-D28 k and parvalbumin in somatic and visceral sensory neurons. Neuroscience 68:883–892
Hunt SP, Rossi J (1985) Peptide and non peptide containing unmyelinated primary afferents: the parallel processing of nociceptive information. Philos Trans R Soc Lond B 308:283–289
Ichikawa H, Helke CJ (1995) Parvalbumin and calbindin D-28 k in vagal and glossopharyngeal sensory neurons of the rat. Brain Res 675:337–341
Ichikawa H, Deguchi T, Fujiyoshi Y, Nakago T, Jacobowitz DM, Sugimoto T (1996) Calbindin-D28k-immunoreactivity in the trigeminal ganglion neurons and molar tooth pulp of the rat. Brain Res 715:71–78
Ju G, Hökfelt T, Brodin E, Fahrenkrug J, Fischer JA, Frey P, Elde RP, Brown JC (1987) Primary sensory neurons of the rat showing calcitonin gene-related peptide immunoreactivity and their relation to substance P-, somatostatin-, galanin-, vasoactive intestinal polypeptide- and cholecystokinin-immunoreactive ganglion cells. Cell Tissue Res 247:417–431
Kai-Kai MA (1989) Cytochemistry of the trigeminal and dorsal root ganglia and spinal cord of the rat. Comp Biochem Physiol 93A:183–193
Kashiba H, Senba E, Ueda Y, Tohyama M (1990) Calbindin D28k-containing splanchnic and cutaneous dorsal root ganglion neurons of the rat. Brain Res 528:311–316
Laasberg T (1990) Ca2+-mobilizing receptors of gastrulating chick embryo. Comp Biochem Physiol C97:1–12
Lee Y, Kawai Y, Shiosaka S, Takami K, Kiyama H, Hillyard CJ, Girgis S, MacIntyre I, Emson PC, Tohyama M (1985) Coexistence of calcitonin gene-related peptide and substance P-like peptide in single cells of the trigeminal ganglion of the rat: immunocytochemical analysis. Brain Res 330:194–196
Lewis C, Neidhart S, Holy C, North RA, Buell G, Suprenant A (1995) Coexpression of P2X2 and P2X3 receptor subunits can account for ATP-gated currents in sensory neurons. Nature 377:432–434
Liu M, King BF, Dunn PM, Rong W, Townsend-Nicholson A, Burnstock G (2001) Coexpression of P2X(3) and P2X(2) receptor subunits in varying amounts generates heterogeneous populations of P2X receptors that evoke a spectrum of agonist responses comparable to that seen in sensory neurons. J Pharmacol Exp Ther 296:1043–1050
Llewellyn-Smith IJ, Burnstock G (1998) Ultrastructural localization of P2X3 receptors in rat sensory neurons. Neuroreport 9:2245–2250
McMahon SB, Armanini MP, Ling LH, Phillips HS (1994) Expression and coexpression of Trk receptors in subpopulations of adult primary sensory neurons projecting to identified peripheral targets. Neuron 12:1161–1171
Novakovic SD, Kassotakis LC, Oglesby IB, Smith JAM, Eglen RM, Ford APDW, Hunter JC (1999) Immunocytochemical localization of P2X3 purinoceptors in sensory neurons in naive rats and following neuropathic injury. Pain 80:273–282
Ralevic V, Burnstock G (1998) Receptors for purines and pyrimidines. Pharmacol Rev 50:413–492
Rong W, Burnstock G, Spyer KM (2000) P2X purinoceptor-mediated excitation of trigeminal lingual nerve terminals in an in vitro intra-arterially perfused rat tongue preparation. J Physiol 524:891–902
Rong W, Spyer KM, Burnstock G (2002) Activation and sensitisation of low and high threshold afferent fibres mediated by P2X receptors in the mouse urinary bladder. J Physiol 541:591–600
Silverman JD, Kruger L (1988) Lectin and neuropeptide labeling of separate populations of dorsal rat testis and cornea whole mount preparations. Somatosens Res 5:259–267
Silverman JD, Kruger L (1990) Selective neuronal glycoconjugate expression in sensory and autonomic ganglia: relation of lectin reactivity to peptide and enzyme markers. J Neurocytol 19:789–801
Snider WD, McMahon SB (1998) Tackling pain at the source: new insights into nociceptors. Neuron 20:629–632
Souslova V, Cesare P, Ding Y, Akopian AN, Stanfa L, Suzuki R, Carpenter K, Dickenson A, Boyce S, Hill R, Nebenuis-Oosthuizen D, Smith AJ, Kidd EJ, Wood JN (2000) Warm-coding deficits and aberrant inflammatory pain in mice lacking P2X3 receptors. Nature 407:1015–1017
Ueno S, Tsuda M, Iwanaga T, Inoue K (1999) Cell type-specific ATP-activated responses in rat dorsal root ganglion neurons. Br J Pharmacol 126:429–436
Vlaskovska M, Kasakov L, Rong W, Bodin P, Bardini M, Cockayne DA, Ford AP, Burnstock G (2001) P2X3 knock-out mice reveal a major sensory role for urothelially released ATP. J Neurosci 21:5670–5677
Vulchanova L, Arvidsson U, Riedl M, Wang J, Buell G., Surprenant A, North RA, Elde R (1997) Immunocytochemical study of the P2X2 and P2X3 receptor subunits in rat and monkey sensory neurons and their central terminals. Neuropharmacology 36:1229–1242
Vulchanova L, Riedl MS, Shuster SJ, Stone LS, Hargreaves KM, Buell G., Surprenant, A, North RA, Elde R (1998) P2X3 is expressed by DRG neurons that terminate in inner lamina II. Eur J Neurosci 10:3470–3478
Wakisaka S, Takikita S, Youn SH, Kurisu K (1996) Partial coexistence of neuropeptide Y and calbindin D28 k in the trigeminal ganglion following peripheral axotomy of the inferior alveolar nerve in the rat. Brain Res 707:228–234
Wang H, Rivero Melian C, Robertson B, Grant G (1994) Transganglionic transport and binding of the isolectin B4 from Griffonia simplicifolia I in rat primary sensory neurons. Neuroscience 62:539–551
Xiang Z, Bo X, Burnstock G (1998) Localization of ATP-gated P2X receptor immunoreactivity in rat sensory and sympathetic ganglia. Neurosci Lett 256:105–108
Zhong Y, Dunn PM, Bardini M, Ford AP, Cockayne DA, Burnstock G (2001) Changes in P2X receptor responses of sensory neurons from P2X3-deficient mice. Eur J Neurosci 14:1784–1792
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ruan, H.Z., Moules, E. & Burnstock, G. Changes in P2X3 purinoceptors in sensory ganglia of the mouse during embryonic and postnatal development. Histochem Cell Biol 122, 539–551 (2004). https://doi.org/10.1007/s00418-004-0714-9
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00418-004-0714-9