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P2X(7) receptors in the enteric nervous system of guinea-pig small intestine.
J Comp Neurol. 2001 Nov 19; 440(3):299-310.JC

Abstract

The P2X(7) purinergic receptor subtype has been cloned and emphasized as a prototypic P2Z receptor involved in neurotransmission in the central nervous system and ATP-mediated lysis of macrophages in the immune system. Less is known about the neurobiology of P2X(7) receptors in the enteric nervous system (ENS). We studied the distribution of the receptor with indirect immunofluorescence and used selective agonists and antagonists to analyze pharmacologic aspects of its electrophysiologic behavior as determined with intracellular "sharp" microelectrodes and patch-clamp recording methods in neurons identified morphologically by biocytin injection in the ENS. Application of ATP or 2'- (or-3'-) O-(4-benzoylbenzoyl) adenosine 5'-triphosphate (BzBzATP) activated an inward current in myenteric neurons. Brilliant blue G, a selective P2X(7) antagonist, suppressed the responses to both agonists. Potency of the antagonist was greatest (smaller IC(50)) for the current evoked by BzBzATP. The P2X(7) antagonists 1-[N,O-bis (1,5-isoquinolinesulfonyl)-N-methyl-l-tyrosyl]-4-piperazine (KN-62) and oxidized ATP also suppressed the BzBzATP-activated current. Micropressure application of BzBzATP evoked rapidly activating depolarizing responses in intracellular studies with "sharp" microelectrodes. Oxidized-ATP suppressed these responses in both myenteric and submucosal neurons. Rapidly activating depolarizing responses evoked by application of nicotinic, serotonergic 5-HT(3), or gamma-aminobutyric acid A (GABA(A)) receptor agonists were unaffected by brilliant blue G. Immunoreactivity for the P2X(7) receptor was widely distributed surrounding ganglion cell bodies and associated with nerve fibers in both myenteric and submucous plexuses. P2X(7) immunoreactivity was colocalized with synapsin and synaptophysin and surrounded ganglion cells that contained either calbindin, calretinin, neuropeptide Y, substance P, or nitric oxide synthase. The mucosa, submucosal blood vessels, and the circular muscle coat also showed P2X(7) receptor immunoreactivity.

Authors+Show Affiliations

Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, Ohio 43210-1218, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11745625

Citation

Hu, H Z., et al. "P2X(7) Receptors in the Enteric Nervous System of Guinea-pig Small Intestine." The Journal of Comparative Neurology, vol. 440, no. 3, 2001, pp. 299-310.
Hu HZ, Gao N, Lin Z, et al. P2X(7) receptors in the enteric nervous system of guinea-pig small intestine. J Comp Neurol. 2001;440(3):299-310.
Hu, H. Z., Gao, N., Lin, Z., Gao, C., Liu, S., Ren, J., Xia, Y., & Wood, J. D. (2001). P2X(7) receptors in the enteric nervous system of guinea-pig small intestine. The Journal of Comparative Neurology, 440(3), 299-310.
Hu HZ, et al. P2X(7) Receptors in the Enteric Nervous System of Guinea-pig Small Intestine. J Comp Neurol. 2001 Nov 19;440(3):299-310. PubMed PMID: 11745625.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - P2X(7) receptors in the enteric nervous system of guinea-pig small intestine. AU - Hu,H Z, AU - Gao,N, AU - Lin,Z, AU - Gao,C, AU - Liu,S, AU - Ren,J, AU - Xia,Y, AU - Wood,J D, PY - 2001/12/18/pubmed PY - 2002/1/12/medline PY - 2001/12/18/entrez SP - 299 EP - 310 JF - The Journal of comparative neurology JO - J Comp Neurol VL - 440 IS - 3 N2 - The P2X(7) purinergic receptor subtype has been cloned and emphasized as a prototypic P2Z receptor involved in neurotransmission in the central nervous system and ATP-mediated lysis of macrophages in the immune system. Less is known about the neurobiology of P2X(7) receptors in the enteric nervous system (ENS). We studied the distribution of the receptor with indirect immunofluorescence and used selective agonists and antagonists to analyze pharmacologic aspects of its electrophysiologic behavior as determined with intracellular "sharp" microelectrodes and patch-clamp recording methods in neurons identified morphologically by biocytin injection in the ENS. Application of ATP or 2'- (or-3'-) O-(4-benzoylbenzoyl) adenosine 5'-triphosphate (BzBzATP) activated an inward current in myenteric neurons. Brilliant blue G, a selective P2X(7) antagonist, suppressed the responses to both agonists. Potency of the antagonist was greatest (smaller IC(50)) for the current evoked by BzBzATP. The P2X(7) antagonists 1-[N,O-bis (1,5-isoquinolinesulfonyl)-N-methyl-l-tyrosyl]-4-piperazine (KN-62) and oxidized ATP also suppressed the BzBzATP-activated current. Micropressure application of BzBzATP evoked rapidly activating depolarizing responses in intracellular studies with "sharp" microelectrodes. Oxidized-ATP suppressed these responses in both myenteric and submucosal neurons. Rapidly activating depolarizing responses evoked by application of nicotinic, serotonergic 5-HT(3), or gamma-aminobutyric acid A (GABA(A)) receptor agonists were unaffected by brilliant blue G. Immunoreactivity for the P2X(7) receptor was widely distributed surrounding ganglion cell bodies and associated with nerve fibers in both myenteric and submucous plexuses. P2X(7) immunoreactivity was colocalized with synapsin and synaptophysin and surrounded ganglion cells that contained either calbindin, calretinin, neuropeptide Y, substance P, or nitric oxide synthase. The mucosa, submucosal blood vessels, and the circular muscle coat also showed P2X(7) receptor immunoreactivity. SN - 0021-9967 UR - https://www.unboundmedicine.com/medline/citation/11745625/P2X_7__receptors_in_the_enteric_nervous_system_of_guinea_pig_small_intestine_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0021-9967&date=2001&volume=440&issue=3&spage=299 DB - PRIME DP - Unbound Medicine ER -