PREJUNCTIONAL AND POSTJUNCTIONAL EFFECTS OF DIADENOSINE POLYPHOSPHATES IN THE GUINEA-PIG VAS-DEFERENS

The pre- and postjunctional activities of a number of diadenosine poly phosphates were examined in the guinea-pig isolated vas deferens at th e level of the membrane potential, using a modified sucrose-gap techni que. P-1,P-3-Di(adenosine 5')triphosphate (Ap(3)A), P-1,P-4-di(adenosi ne 5')tetraphosphate (Ap(4)A) and P-1,P-5-di(adenosine 5')pentaphospha te (Ap(5)A) all caused concentration-dependent depolarization of the s mooth muscle membrane. The potency order was: Ap(5)A > Ap(4)A greater than or equal to Ap(3)A. P-1,P-2-Di(adenosine 5')pyrophosphate (Ap(2)A ) did not evoke depolarization even at the highest concentration teste d (1 mM). All the dinucleotides caused a reduction in the amplitude of evoked excitatory junction potentials (e.j.ps). The potency order was : Ap(5)A = Ap(4)A > Ap(3)A > Ap(2)A. The depolarizations evoked by the dinucleotides were markedly reduced by the selective P-2X-purinocepto r antagonist, pyridoxalphosphate-6-azophenyl-2'.4'-disulphonic acid (P PADS, 10 mu M), as was the amplitude of the fully facilitated e.j.p. T he inhibition of the e.j.p. evoked by Ap(3)A and Ap(2)A was reduced by the P-1-purinoceptor antagonist, 8-p-sulphophenyltheophylline (8-pSPT , 50 mu M), but that evoked by Ap(5)A and Ap(4)A was not. Thus, Ap(3)A , Ap(4)A and Ap(5)A evoke depolarization of the guinea-pig vas deferen s via P-2X-purinoceptors, and additionally Ap(2)A and Ap(3)A exert a p rejunctional effect via P-1-purinoceptors. The prejunctional activity of Ap(4)A and Ap(5)A is mediated via an undefined purinoceptor, which is neither P-1 nor P-2X.