Evidence that the inhibition of ATP release from sympathetic nerves by adenosine is a physiological mechanism.

1. Perfusion with the P1-purinoceptor agonist adenosine (1-500 microM) greatly reduced the stimulation-induced release of ATP and the initial contractile phase of the response of the guinea pig vas deferens to field stimulation. 2. The inhibitory effects of adenosine (100 microM) were readily antagonised by the P1-purinoceptor antagonist, 8-phenyltheophylline (10 microM). 3. Dipyridamole (10 microM), inhibited the stimulation-evoked release of ATP from the guinea pig vas deferens and reduced the initial component of contraction. 4. These results support the view that adenosine, resulting from ectoenzymatic breakdown of ATP released as a cotransmitter from sympathetic nerve terminals, acts as a physiological prejunctional regulator of transmitter release.