Adenosine, AMP, ADP, and ATP were approximately equipotent in inhibiting contractions evoked by field stimulation (10 Hz, 60 V, 1 ms, 10 s) of isolated preparations of rat cauda epididymis. Adenosine had no significant effect on contractions induced by the exogenous application of either noradrenaline or ATP. 2. The effects of adenosine and AMP were markedly potentiated by the adenosine uptake inhibitor, dipyridamole. In contrast there was only a two-fold potentiation of the effects of ATP and no potentiation of the effects of ADP by dipyridamole. 3. Inhibitory responses to both adenosine and ATP were blocked by 8-phenyltheophylline. Neither the P2Y-purinoceptor antagonist, reactive blue 2, nor P2X purinoceptor antagonist alpha,beta-methylene ATP, blocked the inhibitory effects of ATP. 4. Several stable analogues of adenosine, namely 5'-(N-ethyl) carboxamidoadenosine (NECA), N6-cyclohexyl-adenosine (CHA), L-N6-(2-phenyl-isopropyl)adenosine (L-PIA), D-N6-(2-phenyl-isopropyl)adenosine (D-PIA) and 2-chloroadenosine (CADO) also inhibited nerve stimulation-induced contractions. NECA was the most potent. L-PIA and D-PIA were approximately equipotent, except in the presence of dipyridamole, when the potency of L-PIA exceeded that of D-PIA. 5. Field stimulation-induced contractions of the rat cauda epididymis were unaffected by the alpha 2-adrenoceptor agonists clonidine and xylazine; isoprenaline in high concentrations produced phentolamine-sensitive inhibition of contractions evoked by field stimulation and exogenous application of noradrenaline. 6. These findings taken together are consistent with the possibility that prejunctional purinoceptors, which are atypical in that they are directly activated by both ATP and adenosine, mediate inhibition of neurotransmission in this tissue. No evidence for the presence of functional alpha 2-adrenoceptors modulating neurotransmission was obtained.
