Multiple P2X receptors on guinea‐pig pelvic ganglion neurons exhibit novel pharmacological properties

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 μ M was 46±27% (range 0 – 100%) of that evoked by ATP 100 μ M in the same cell. Cross‐desensitization indicated the presence of αβmeATP‐sensitive and ‐insensitive receptors. The concentration‐response curve for αβmeATP had an EC 50 of 55 μ M , and a Hill coefficient of 0.99, while at the αβmeATP‐insensitive receptor, ATP had an EC 50 of 73 μ M , 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 Zn 2+ (3 – 300 μ M ) inhibited the responses to αβmeATP and ATP, with IC 50 values of 286 and 60 μ M , respectively. 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.British Journal of Pharmacology (2001) 132 , 221–233; doi: 10.1038/sj.bjp.0703778