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Investigation of the actions of PPADS, a novel P 2X ‐purinoceptor antagonist, in the guinea‐pig isolated vas deferens
Author(s) -
McLaren G.J.,
Lambrecht G.,
Mutschler E.,
Bäumert H.G.,
Sneddon P.,
Kennedy C.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb14825.x
Subject(s) - ppads , purinergic receptor , endocrinology , vas deferens , depolarization , medicine , agonist , carbachol , antagonist , p2 receptor , chemistry , stimulation , biology , receptor , adenosine
1 Pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (PPADS) was investigated for its ability to act as an antagonist at P 2X ‐purinoceptors which mediate neurogenic excitatory junction potentials (e.j.ps) and contractions in the guinea‐pig isolated vas deferens. 2 PPADS (10 −7 m ) caused a small potentiation of the phasic, predominantly purinergic component of contractions evoked by symapthetic nerve stimulation, but higher concentrations of PPADS (3 × 10 −6 –3 × 10 −5 m ) elicited a substantial and significant concentration‐dependent inhibition. In contrast, over the same concentration‐range, PPADS had no effect on the tonic, predominantly noradrenergic phase. 3 PPADS (3 × 10 −;5 m ) also inhibited contractile responses to exogenous α,β‐methyleneATP (10 −8 –10 −3 m ), a P 2X ‐purinoceptor agonist, without affecting the responses to exogenous noradrenaline (10 −8 −10 −3 m ), carbachol (10 −5 m ) or histamine (10 −4 m ). 4 PPADS (10 −7 –3 × 10 −5 m ) produced a concentration‐dependent reduction in e.j.p. magnitude and resting membrane potential. The maximum effect was seen at 10 −5 m PPADS, which reduced e.j.p. magnitude from 13.7 ± 0.6 mV ( n = 12) to 1.8 ± 0.7 mV ( n = 12) and membrane potential from − 64.8 ± 0.6 mV ( n = 51) to − 55.0 ± 1.8 mV ( n = 12). 5 The PPADS‐induced depolarization was not inhibited by the P 2X ‐purinoceptor antagonist, suramin (10 −4 m ). This indicates that the depolarization was not due to an agonist action of PPADS at P 2X ‐purinoceptors. 6 The results support the proposal that PPADS is a selective antagonist at P 2X purinoceptors as opposed to non‐P 2 ‐purinoceptors in the guinea‐pig vas deferens, but its ability to cause membrane depolarization independently of P 2X ‐purinoceptors and also, at a low concentration, to potentiate the phasic component of the neurogenic contraction indicates that it has other actions.