A study of the actions of P1-purinoceptor agonists and antagonists in the mouse vas deferens in vitro.

1. We have examined the effects of purinoceptor agonists and antagonists on the mechanical 'twitch' response, excitatory junction potential (e.j.p.) amplitude and [3H]-noradrenaline overflow in the mouse vas deferens. 2. The agonist profile for inhibition of the mechanical response was N6-([R]-2-phenylisopropyl)adenosine (L-PIA) congruent to N6-cyclohexyladenosine (CHA) greater than 5' N-ethylcarboxamido-adenosine (NECA) greater than 2-chloroadenosine (2ClA) congruent N6-([S]-2-phenylisopropyl)adenosine (D-PIA). 3. The P1-purinoceptor agonists inhibited the e.j.p. with an agonist profile of CHA greater than L-PIA congruent to NECA greater than 2ClA. 4. 2ClA inhibited [3H]-noradrenaline overflow with an EC50 of 1.2 microM which was not significantly different from the values for inhibition of the e.j.p. and the mechanical response. 5. The inhibitory action of 2ClA on the mechanical response was antagonized by 5 microM 8-phenyltheophylline (8-PT). However, neither blockade of P1-purinoceptors by 8-PT nor increasing the rate of degradation of endogenous adenosine by addition of adenosine deaminase had any effect on the mechanical response per se. 8-PT (5 microM) also failed to alter the e.j.p. amplitude or [3H]-noradrenaline overflow. 6. These results indicate that there are P1-purinoceptors present on sympathetic nerve terminals of the mouse vas deferens which are more like A1- than A2-receptors, but may be better classified as being of the A3-subtype (Ribeiro & Sebastiao, 1986). These receptors are not normally involved in the feedback regulation of transmitter release in this tissue.