Pre- and postjunctional effects of diadenosine polyphosphates in the guinea-pig vas deferens

The pre- and postjunctional activities of a number of diadenosine polyphosphates were examined in the guinea-pig isolated vas deferens at the level of the membrane potential, using a modified sucrose-gap technique. P1,P3-Di(adenosine 5')triphosphate (Ap3A), P1,P4-di(adenosine 5')tetraphosphate (Ap4A) and P1,P5-di(adenosine 5')pentaphosphate (Ap5A) all caused concentration-dependent depolarization of the smooth muscle membrane. The potency order was: Ap5A > Ap4A > or = Ap3A. P1,P2-Di(adenosine 5')pyrophosphate (Ap2A) did not evoke depolarization even at the highest concentration tested (1 mM). All the dinucleotides caused a reduction in the amplitude of evoked excitatory junction potentials (e.j.ps). The potency order was: Ap5A = Ap4A > Ap3A > Ap2A. The depolarizations evoked by the dinucleotides were markedly reduced by the selective P2X-purinoceptor antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 10 microM), as was the amplitude of the fully facilitated e.j.p. The inhibition of the e.j.p. evoked by Ap3A and Ap2A was reduced by the P1-purinoceptor antagonist, 8-p-sulphophenyltheophylline (8-pSPT, 50 microM), but that evoked by Ap5A and Ap4A was not. Thus, Ap3A, Ap4A and Ap5A evoke depolarization of the guinea-pig vas deferens via P2X-purinoceptors, and additionally Ap2A and Ap3A exert a prejunctional effect via P1-purinoceptors. The prejunctional activity of Ap4A and Ap5A is mediated via an undefined purinoceptor, which is neither P1 nor P2X.