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Distribution of P2Y2 receptors in the guinea pig enteric nervous system and its coexistence with P2X2 and P2X3 receptors, neuropeptide Y, nitric oxide synthase and calretinin

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Abstract

The distribution of P2Y2 receptor-immunoreactive (ir) neurons and fibers and coexistence of P2Y2 with P2X2 and P2X3 receptors, neuropeptide Y (NPY), calretinin (CR), calbindin (CB) and nitric oxide synthase (NOS) was investigated with immunostaining methods. The results showed that P2Y2-ir neurons and fibers were distributed widely in myenteric and submucous plexuses of the guinea pig stomach corpus, jejunum, ileum and colon. The typical morphology of P2Y2-ir neurons was a long process with strong positive staining on the same side of the cell body. The P2Y2-ir neurons could be Dogiel type 1. About 40–60% P2X3-ir neurons were immunoreactive for P2Y2 in the myenteric plexus and all the P2X3-ir neurons expressed the P2Y2 receptor in the submucosal plexus; almost all the NPY-ir neurons and the majority of CR-ir neurons were also immunoreactive for P2Y2, especially in the myenteric plexus of the small intestine; no P2Y2-ir neurons were immunoreactive for P2X2 receptors, CB and NOS. It is shown for the first time that S type/Dogiel type 1 neurons with fast P2X and slow P2Y receptor-mediated depolarizations could be those neurons expressing both P2Y2-ir and P2X3-ir and that they are widely distributed in myenteric and submucosal plexuses of guinea pig gut.

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References

  • Barajas-Lopez C, Espinosa-Luna R, Gerzanich V (1994) ATP closes a potassium and opens a cationic conductance through different receptors in neurons of guinea pig submucous plexus. J Pharmacol Exp Ther 268:1397–1402

    PubMed  CAS  Google Scholar 

  • Barajas-Lopez C, Espinosa-Luna R, Christofi FL (2000) Changes in intracellular Ca2+ by activation of P2 Rs in submucosal neurons in short-term cultures. Eur J Pharmacol 409:243–257

    Article  PubMed  CAS  Google Scholar 

  • Bian X, Bertrand PP, Bornstein JC (2000) Descending inhibitory reflexes involve P2X receptor-mediated transmission from interneurons to motor neurons in guinea-pig ileum. J Physiol 528:551–560

    Article  PubMed  CAS  Google Scholar 

  • Bian X, Ren J, DeVries M, Schnegelsberg B, Cockayne DA, Ford APDW, Galligan JJ (2003) Peristalsis is impaired in the small intestine of mice lacking the P2X3 subunit. J Physiol 551:309–322

    Article  PubMed  CAS  Google Scholar 

  • Brookes SJ, Steele PA, Costa M (1991) Calretinin immunoreactivity in cholinergic motor neurones, interneurones and vasomotor neurones in the guinea-pig small intestine. Cell Tissue Res 263:471–481

    Article  PubMed  CAS  Google Scholar 

  • Burnstock G (2001) Purinergic signaling in gut. In: Abbracchio MP, Williams M (eds) Handbook of experimental pharmacology. Volume 151/II, Purinergic and pyrimidinergic signaling II, cardiovascular, respiratory, immune, metabolic and gastrointestinal tract function. Springer-Verlag, New York, pp 141–238

  • Burnstock G (2004) Introduction: P2 receptors. Curr Topics Med Chem 4:793–803

    Article  CAS  Google Scholar 

  • Castelucci P, Robbins HL, Poole DP, Furness JB (2002) The distribution of purine P2X2 receptors in the guinea-pig enteric nervous system. Histochem Cell Biol 117:415–422

    Article  PubMed  CAS  Google Scholar 

  • Castelucci P, Robbins HL, Furness JB (2003) P2X2 purine receptor immunoreactivity of intraganglionic laminar endings in the mouse gastrointestinal tract. Cell Tissue Res 312:167–174

    PubMed  CAS  Google Scholar 

  • Christofi FL, Wunderlich J, Yu JG, Wang YZ, Xue J, Guzman J, Javed N, Cooke H (2004) Mechanically evoked reflex electrogenic chloride secretion in rat distal colon is triggered by endogenous nucleotides acting at P2Y1, P2Y2, and P2Y4 receptors. J Comp Neurol 469:16–36

    Article  PubMed  CAS  Google Scholar 

  • Cooke HJ, Xue J, Yu JG, Wunderlich J, Wang YZ, Guzman J, Javed N, Christofi FL (2004) Mechanical stimulation releases nucleotides that activate P2Y1 receptors to trigger neural reflex chloride secretion in guinea pig distal colon. J Comp Neurol 469:1–15

    Article  PubMed  CAS  Google Scholar 

  • Cunningham SM, Lees GM (1995) Neuropeptide Y in submucosal ganglia: regional differences in the innervation of guinea-pig large intestine. J Auton Nerv Syst 55:135–145

    Article  PubMed  CAS  Google Scholar 

  • Furness JB, Trussell DC, Pompolo S, Bornstein JC, Smith TK (1990) Calbindin neurons of the guinea-pig small intestine: quantitative analysis of their numbers and projections. Cell Tissue Res 260:261–272

    Article  PubMed  CAS  Google Scholar 

  • Furness JB, Kunze WA, Bertrand PP, Clerc N, Bornstein JC (1998) Intrinsic primary afferent neurons of the intestine. Prog Neurobiol 54:1–18

    Article  PubMed  CAS  Google Scholar 

  • Furness JB (2000) Types of neurons in the enteric nervous system. J Auton Nerv Syst 81:87–96

    Article  PubMed  CAS  Google Scholar 

  • Galligan JJ, Bertrand PP (1994) ATP mediates fast synaptic potentials in enteric neurons. J Neurosci 14:7563–7571

    PubMed  CAS  Google Scholar 

  • Galligan JJ, LePard KJ, Schneider DA, Zhou X (2000) Multiple mechanisms of fast excitatory synaptic transmission in the enteric nervous system. J Auton Nerv Syst 81:97–103

    Article  PubMed  CAS  Google Scholar 

  • Heinemann A, Shahbazian A, Bartho L, Holzer P (1999) Different receptors mediating the inhibitory action of exogenous ATP and endogenously released purines on guinea-pig intestinal peristalsis. Br J Pharmacol 128:313–320

    Article  PubMed  CAS  Google Scholar 

  • Hu HZ, Gao N, Lin Z, Gao C, Liu S, Ren J, Xia Y, Wood JD (2001) P2X7 receptors in the enteric nervous system of guinea-pig small intestine. J Comp Neurol 440:299–310

    Article  PubMed  CAS  Google Scholar 

  • Hu HZ, Gao N, Zhu MX, Liu S, Ren J, Gao YX, Xia Y, Wood JD (2003) Slow excitatory synaptic transmission mediated by P2Y1 receptors in the guinea-pig enteric nervous system. J Physiol 550:493–504

    Article  PubMed  CAS  Google Scholar 

  • Katayama Y, Morita K (1989) Adenosine 5′-triphosphate modulates membrane potassium conductance in guinea-pig myenteric neurones. J Physiol 408:373–390

    Google Scholar 

  • Khakh BS, Burnstock G, Kennedy C, King BF, North RA, Seguela P, Voigt M, Humphrey PPA (2001) International Union of Pharmacology. XXIV. Current status of the nomenclature and properties of P2X receptors and their subunits. Pharmacol Rev 53:107–118

    PubMed  CAS  Google Scholar 

  • Kimball BC, Yule DI, Mulholland MW (1996) Extracellular ATP mediates Ca2+ signaling in cultured myenteric neurons via a PLC-dependent mechanism. Am J Physiol 270:G587–G593

    PubMed  CAS  Google Scholar 

  • LePard KJ, Galligan JJ (1999) Analysis of fast synaptic pathways in myenteric plexus of guinea pig ileum. Am J Physiol 276:G529–G538

    PubMed  CAS  Google Scholar 

  • LePard KJ, Messori E, Galligan JJ (1997) Purinergic fast excitatory postsynaptic potentials in myenteric neurons of guinea pig: distribution and pharmacology. Gastroenterology 113:1522–1534

    Article  PubMed  CAS  Google Scholar 

  • McConalogue K, Furness JB (1993) Projections of nitric oxide synthesizing neurons in the guinea-pig colon. Cell Tissue Res 271:545–553

    Article  PubMed  CAS  Google Scholar 

  • Monro RL, Bertrand PP, Bornstein JC (2004) ATP participates in three excitatory postsynaptic potentials in the submucous plexus of the guinea pig ileum. J Physiol 556:571–584

    Article  PubMed  CAS  Google Scholar 

  • Nicholas RA (2001) Identification of the P2Y12 receptor: a novel member of the P2Y family of receptors activated by extracellular nucleotides. Mol Pharmacol 60:416–420

    PubMed  CAS  Google Scholar 

  • Nurgali K, Stebbing MJ, Furness JB (2004) Correlation of electrophysiological and morphological characteristics of enteric neurons in the mouse colon. J Comp Neurol 468:112–124

    Article  PubMed  Google Scholar 

  • Oglebsby IB, Lachnit WG, Burnstock G, Ford APDW (1999) Subunit specificity of polyclonal antisera to the carboxy terminal regions of P2X receptors P2X1 through P2X7. Drug Dev Res 47:189–195

    Article  Google Scholar 

  • Phillips RJ, Hargrave SL, Rhodes BS, Zopf DA, Powley TL (2004) Quantification of neurons in the myenteric plexus: an evaluation of putative pan-neuronal markers. J Neurosci Methods 133: 99–107

    Article  PubMed  Google Scholar 

  • Poole DP, Castelucci P, Robbins HL, Chiocchetti R, Furness JB (2002) The distribution of P2X3 purine receptor subunits in the guinea pig enteric nervous system. Auton Neurosci 101:39–47

    Article  PubMed  CAS  Google Scholar 

  • Quinson N, Robbins HL, Clark MJ, Furness JB (2001) Calbindin immunoreactivity of enteric neurons in the guinea-pig ileum. Cell Tissue Res 305:3–9

    Article  PubMed  CAS  Google Scholar 

  • Ralevic V, Burnstock G (1998) Receptors for purines and pyrimidines. Pharmacol Rev 50:413–492

    PubMed  CAS  Google Scholar 

  • Ren J, Bian X, DeVries M, Schnegelsberg B, Cockayne DA, Ford APDW, Galligan JJ (2003) P2X2 subunits contribute to fast synaptic excitation in myenteric neurons of the mice small intestine. J Physiol 552:809–812

    Article  PubMed  CAS  Google Scholar 

  • Spencer NJ, Walsh M, Smith TK (2000) Purinergic and cholinergic neuro-neuronal transmission underlying reflexes activated by mucosal stimulation in the isolated guinea-pig ileum. J Physiol 522:321–331

    Article  PubMed  CAS  Google Scholar 

  • Teramoto N, Szekely L, Pokrovskaja K, Hu LF, Yoshino T, Akagi T, Klein G (1998) Simultaneous detection of two independent antigens by double staining with two mouse monoclonal antibodies. J Virol Methods 73:89–97

    Article  PubMed  CAS  Google Scholar 

  • Uemura S, Pompolo S, Furness JB (1995) Colocalization of neuropeptide Y with other neurochemical markers in the guinea-pig small intestine. Arch Histol Cytol 58:523–536

    Article  PubMed  CAS  Google Scholar 

  • Van Nassauw L, Brouns I, Adriaensen D, Burnstock G, Timmermans JP (2002) Neurochemical identification of enteric neurons expressing P2X3 receptors in the guinea-pig ileum. Histochem Cell Biol 118:193–203

    PubMed  Google Scholar 

  • Xiang Z, Burnstock G (2004a) Development of nerves expressing P2X3 receptors in the myenteric plexus of rat stomach. Histochem Cell Biol 122:111–119

    Article  PubMed  CAS  Google Scholar 

  • Xiang Z, Burnstock G (2004b) P2X2 and P2X3 purinoceptors in the rat enteric nervous system. Histochem Cell Biol 121:169–179

    Article  PubMed  CAS  Google Scholar 

  • Xiang Z, Bo X, Burnstock G (1998) Localization of ATP-gated P2X receptor immunoreactivity in rat sensory and sympathetic ganglia. Neurosci Letts 256:105–108

    Article  CAS  Google Scholar 

  • Zhou X, Galligan JJ (1998) Non-additive interaction between nicotinic cholinergic and P2X purine receptors in guinea-pig enteric neurons in culture. J Physiol 513:685–697

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Dr. Gillian E. Knight and Dr. Chrystalla Orphanides for editorial assistance. This study was supported by Welcome Trust of UK (064931/Z/01/A).

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Second Military Medical University, 200433, Shanghai, People’s Republic of China

    Zhenghua Xiang

  2. Autonomic Neuroscience Centre, Royal Free and University College Medical School, Rowland Hill Street, London, NW3 2PF, UK

    Zhenghua Xiang & Geoffrey Burnstock

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  1. Zhenghua Xiang
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  2. Geoffrey Burnstock
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Correspondence to Geoffrey Burnstock.

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Xiang, Z., Burnstock, G. Distribution of P2Y2 receptors in the guinea pig enteric nervous system and its coexistence with P2X2 and P2X3 receptors, neuropeptide Y, nitric oxide synthase and calretinin. Histochem Cell Biol 124, 379–390 (2005). https://doi.org/10.1007/s00418-005-0043-7

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