NDLI: Multiple P2X receptors on guinea-pig pelvic ganglion neurons exhibit novel pharmacological properties

Content Provider	PubMed Central
Author	Zhong, Yu Dunn, Philip M. Burnstock, Geoffrey
Copyright Year	2001
Abstract	Application of ATP and α,β-methylene ATP (αβmeATP) 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. Slowly-desensitizing responses were characterized pharmacologically. The response to αβmeATP 100 μM was 46±27% (range 0 – 100%) of that evoked by ATP 100 μM in the same cell. Cross-desensitization indicated the presence of αβmeATP-sensitive and -insensitive receptors. The concentration-response curve for αβmeATP had an EC50 of 55 μM, and a Hill coefficient of 0.99, while at the αβmeATP-insensitive receptor, ATP had an EC50 of 73 μM, with a Hill coefficient of 1.78. The response to αβmeATP was blocked by pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS), suramin and Cibacron blue. However, the αβmeATP-insensitive receptor was inhibited by PPADS, but not by the other two antagonists. 2′- (or 3′-) O-trinitrophenyl-ATP was 10 times more potent in inhibiting responses to αβmeATP than to ATP (at the αβmeATP-insensitive receptor). Lowering extracellular pH potentiated responses to αβmeATP and ATP, while raising pH attenuated them. Co-application of Zn2+ (3 – 300 μM) inhibited the responses to αβmeATP and ATP, with IC50 values of 286 and 60 μM, respectively. In conclusion, unlike rat and mouse pelvic ganglion neurons, which only express P2X2 homomers, at least three distinct P2X receptors are present in guinea-pig pelvic neurons, probably homomeric P2X2, P2X3 and heteromeric P2X2/3 receptors. However, some of the novel pharmacological properties observed suggest that the guinea-pig P2X receptor subtypes may differ from their rat orthologues.
Related Links	http://dx.doi.org/10.1038/sj.bjp.0703778
Ending Page	233
Page Count	13
Starting Page	221
File Format	PDF
ISSN	00071188
Journal	British Journal of Pharmacology
Issue Number	1
Volume Number	132
Language	English
Publisher Date	2001-01-01
Access Restriction	Open
Subject Keyword	Pharmacology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Pharmacology

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