Control of transmitter release in guinea-pig vas deferens by prejunctional P1-purinoceptors

The specific P1-purinoceptor agonist 2-chloroadenosine (3 X 10(-7) M to 3 X 10(-6) M) reduced the magnitude of excitatory junction potentials (e.j.p.s) recorded from guinea-pig vas deferens in response to field stimulation of the sympathetic nerves, but did not have any direct effect on the resting membrane potential. Trains of pulses (2-16 Hz) for 20 s produced a biphasic contractile response, both phases of which were reduced by 2-chloroadenosine (10(-7) to 10(-5) M) by up to 45%. In contrast, the same concentrations of 2-chloroadenosine enhanced by about 20% the contractile response of the vas deferens to exogenously applied adenosine 5'-triphosphate (ATP) and noradrenaline (NA). The specific P1-purinoceptor antagonist 8-phenyltheophylline (8-PT) reversed the inhibitory effect of 2-chloroadenosine on e.j.p. magnitude, partially reversed the inhibitory action of 2-chloroadenosine on both phases of the contractile response to nerve stimulation, and partially reversed the enhancing effect of 2-chloroadenosine on responses to exogenous ATP and NA. We propose that release of ATP and NA (as cotransmitters) from sympathetic nerves can be modulated by prejunctional P1-purinoceptors.