INVESTIGATION OF THE ACTIONS OF PPADS, A NOVEL P-2X-PURINOCEPTOR ANTAGONIST, IN THE GUINEA-PIG ISOLATED VAS-DEFERENS

1 Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) was in vestigated for its ability to act as an antagonist at P-2x-purinocepto rs which mediate neurogenic excitatory junction potentials (e.j.ps) an d contractions in the guinea-pig isolated vas deferens. 2 PPADS (10(-7 ) M) caused a small potentiation of the phasic, predominantly purinerg ic component of contractions evoked by symapthetic nerve stimulation, but higher concentrations of PPADS (3 x 10-(6) x 10(-5) M) elicited a substantial and significant concentration-dependent inhibition. In con trast, over the same concentration-range, PPADS had no effect on the t onic, predominantly noradrenergic phase. 3 PPADS (3 x 10-(5) M) also i nhibited contractile responses to exogenous alpha,beta-methyleneATP (1 0(-8)-10(-3) M), a P-2x-purinoceptor agonist, without affecting the re sponses to exogenous noradrenaline (10(-8)-10(-3) M), carbachol (10(-5 ) M) or histamine (10(-4) M).