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Multiple P2X receptors on guinea-pig pelvic ganglion neurons exhibit novel pharmacological properties.
Br J Pharmacol 2001; 132(1):221-33BJ

Abstract

1. Application of ATP and alpha,beta-methylene ATP (alpha beta meATP) to voltage-clamped guinea-pig pelvic neurons produced three types of inward currents. A fast-desensitizing response was present in 5% (25/660) of neurons, 70% gave slowly-desensitizing currents, and the remainder had biphasic responses. 2. Slowly-desensitizing responses were characterized pharmacologically. The response to alpha beta meATP 100 microM was 46+/-27% (range 0--100%) of that evoked by ATP 100 microM in the same cell. Cross-desensitization indicated the presence of alpha beta meATP-sensitive and -insensitive receptors. 3. The concentration-response curve for alpha beta meATP had an EC(50) of 55 microM, and a Hill coefficient of 0.99, while at the alpha beta meATP-insensitive receptor, ATP had an EC(50) of 73 microM, with a Hill coefficient of 1.78. 4. The response to alpha beta meATP was blocked by pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), suramin and Cibacron blue. However, the alpha beta meATP-insensitive receptor was inhibited by PPADS, but not by the other two antagonists. 5. 2'- (or 3'-) O-trinitrophenyl-ATP was 10 times more potent in inhibiting responses to alpha beta meATP than to ATP (at the alpha beta meATP-insensitive receptor). 6. Lowering extracellular pH potentiated responses to alpha beta meATP and ATP, while raising pH attenuated them. 7. Co-application of Zn(2+) (3--300 microM) inhibited the responses to alpha beta meATP and ATP, with IC(50) values of 286 and 60 microM, respectively. 8. In conclusion, unlike rat and mouse pelvic ganglion neurons, which only express P2X(2) homomers, at least three distinct P2X receptors are present in guinea-pig pelvic neurons, probably homomeric P2X(2), P2X(3) and heteromeric P2X(2/3) receptors. However, some of the novel pharmacological properties observed suggest that the guinea-pig P2X receptor subtypes may differ from their rat orthologues.

Authors+Show Affiliations

Autonomic Neuroscience Institute, Department of Anatomy and Developmental Biology, Royal Free and University College Medical School, Rowland Hill Street, London, NW3 2PF. yzhong@ucl.ac.ukNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11156581

Citation

Zhong, Y, et al. "Multiple P2X Receptors On Guinea-pig Pelvic Ganglion Neurons Exhibit Novel Pharmacological Properties." British Journal of Pharmacology, vol. 132, no. 1, 2001, pp. 221-33.
Zhong Y, Dunn PM, Burnstock G. Multiple P2X receptors on guinea-pig pelvic ganglion neurons exhibit novel pharmacological properties. Br J Pharmacol. 2001;132(1):221-33.
Zhong, Y., Dunn, P. M., & Burnstock, G. (2001). Multiple P2X receptors on guinea-pig pelvic ganglion neurons exhibit novel pharmacological properties. British Journal of Pharmacology, 132(1), pp. 221-33.
Zhong Y, Dunn PM, Burnstock G. Multiple P2X Receptors On Guinea-pig Pelvic Ganglion Neurons Exhibit Novel Pharmacological Properties. Br J Pharmacol. 2001;132(1):221-33. PubMed PMID: 11156581.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multiple P2X receptors on guinea-pig pelvic ganglion neurons exhibit novel pharmacological properties. AU - Zhong,Y, AU - Dunn,P M, AU - Burnstock,G, PY - 2001/1/13/pubmed PY - 2001/6/2/medline PY - 2001/1/13/entrez SP - 221 EP - 33 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 132 IS - 1 N2 - 1. Application of ATP and alpha,beta-methylene ATP (alpha beta meATP) to voltage-clamped guinea-pig pelvic neurons produced three types of inward currents. A fast-desensitizing response was present in 5% (25/660) of neurons, 70% gave slowly-desensitizing currents, and the remainder had biphasic responses. 2. Slowly-desensitizing responses were characterized pharmacologically. The response to alpha beta meATP 100 microM was 46+/-27% (range 0--100%) of that evoked by ATP 100 microM in the same cell. Cross-desensitization indicated the presence of alpha beta meATP-sensitive and -insensitive receptors. 3. The concentration-response curve for alpha beta meATP had an EC(50) of 55 microM, and a Hill coefficient of 0.99, while at the alpha beta meATP-insensitive receptor, ATP had an EC(50) of 73 microM, with a Hill coefficient of 1.78. 4. The response to alpha beta meATP was blocked by pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), suramin and Cibacron blue. However, the alpha beta meATP-insensitive receptor was inhibited by PPADS, but not by the other two antagonists. 5. 2'- (or 3'-) O-trinitrophenyl-ATP was 10 times more potent in inhibiting responses to alpha beta meATP than to ATP (at the alpha beta meATP-insensitive receptor). 6. Lowering extracellular pH potentiated responses to alpha beta meATP and ATP, while raising pH attenuated them. 7. Co-application of Zn(2+) (3--300 microM) inhibited the responses to alpha beta meATP and ATP, with IC(50) values of 286 and 60 microM, respectively. 8. In conclusion, unlike rat and mouse pelvic ganglion neurons, which only express P2X(2) homomers, at least three distinct P2X receptors are present in guinea-pig pelvic neurons, probably homomeric P2X(2), P2X(3) and heteromeric P2X(2/3) receptors. However, some of the novel pharmacological properties observed suggest that the guinea-pig P2X receptor subtypes may differ from their rat orthologues. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/11156581/Multiple_P2X_receptors_on_guinea_pig_pelvic_ganglion_neurons_exhibit_novel_pharmacological_properties_ L2 - https://doi.org/10.1038/sj.bjp.0703778 DB - PRIME DP - Unbound Medicine ER -