Effects of A(1)-adenosine receptor antagonists on purinergic transmission in the guinea-pig vas deferens in vitro

1 Intracellularly recorded excitatory junction potentials (e.j.ps) were use d to study the effects of adenosine receptor antagonists on neurotransmitte r release from postganglionic sympathetic nerve terminals in the guinea-pig vas deferens in vitro. 2 The A(1) adenosine receptor antagonists, 8-phenyltheophylline (10 mu M) a nd 8-cyclopentyl-1,3-dipropylxanthine (0.1 mu M), increased the amplitude o f e.j.ps evoked during trains of 20 stimuli at 1 Hz in the presence, but no t in the absence, of the alpha(2)-adrenoceptor antagonist, yohimbine (1 mu M) or the non-selective alpha-adrenoceptor antagonist, phentolamine (1 mu M ). 3 Adenosine (100 mu M) reduced the amplitude of e.j.ps, both in the presenc e and in the absence of phentolamine (1 mu M). This inhibitory effect of ad enosine is most likely caused by a reduction in transmitter release as ther e was no detectable change in spontaneous e.j.p. amplitudes. 4 In the presence of phentolamine, application of the adenosine uptake inhi bitor, S-(p-nitrobenzyl)-6-thioinosine (0.1 mu M), had no effect on e.j.p. amplitudes. 5 The phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (100 mu M), significantly increased the amplitudes of all e.j.ps evoked during trains o f 20 stimuli at 1 Hz, both in the presence and in the absence of phentolami ne (1 mu M). 6 These results suggest that endogenous adenosine modulates neurotransmitte r release by an action at prejunctional A(1) adenosine receptors only when alpha(2)-adrenoceptors are blocked.