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 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 x 10-(6) x 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 x 10-(5) M) also inhibited contractile responses to exogenous alpha,beta-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).