P-1-PURINOCEPTOR-MEDIATED MODULATION OF NEURAL NORADRENALINE AND ATP RELEASE IN GUINEA-PIG VAS-DEFERENS

The effect of P-1-purinoceptor activation on contractions, release of noradrenaline and release of ATP elicited by electrical field stimulat ion (210 pulses, 7 Hz) was studied in the superfused vas deferens of t he guinea pig. Release of noradrenaline was assessed as overflow of to tal tritium after preincubation with [H-3]-noradrenaline. ATP was meas ured by means of the luciferinluciferase technique. Electrical stimula tion elicited reproducible contraction, tritium overflow and ATP overf low. In the absence of other drugs, adenosine (10-100 mu M) did not ch ange evoked contractions but reduced the evoked overflow of tritium an d ATP. In subsequent experiments alpha(1)-adrenoceptors were blocked b y prazosin, P-2-purinoceptors by suramin and alpha(2)-adrenoceptors by rauwolscine. No or almost no contraction remained under these conditi ons. The evoked overflow of tritium was 505% and the evoked overflow o f ATP 34% of that observed in the absence of prazosin, suramin and rau wolscine. Adenosine (1-100 mu M) again reduced the evoked overflow of tritium and ATP, and so did the A(1)-selective agonist 2-chloro-N-6-cy clopentyladenosine (CCPA; 0.032-0.32 mu M). Adenosine and CCPA decreas ed the evoked overflow of ATP to a greater extent than the evoked over flow of tritium. It is concluded that neural release of both postgangl ionic sympathetic cotransmitters, noradrenaline and ATP, is decreased upon activation of prejunctional P-1- (A(1)-) purinoceptors in guinea- pig vas deferens. The A(1) -receptor-mediated inhibition of the releas e of ATP is more marked than the inhibition of the release of noradren aline, a pattern opposite to the inhibition produced by activation of prejunctional alpha(2)-autoreceptors.