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

Intracellularly recorded excitatory junction potentials (e.j.ps) were used to study the effects of adenosine receptor antagonists on neurotransmitter release from postganglionic sympathetic nerve terminals in the guinea‐pig vas deferens in vitro . The A 1 adenosine receptor antagonists, 8‐phenyltheophylline (10 μ M ) and 8‐cyclopentyl‐1,3‐dipropylxanthine (0.1 μ M ), increased the amplitude of e.j.ps evoked during trains of 20 stimuli at 1 Hz in the presence, but not in the absence, of the α 2 ‐adrenoceptor antagonist, yohimbine (1 μ M ) or the non‐selective α‐adrenoceptor antagonist, phentolamine (1 μ M ). Adenosine (100 μ M ) reduced the amplitude of e.j.ps, both in the presence and in the absence of phentolamine (1 μ M ). This inhibitory effect of adenosine is most likely caused by a reduction in transmitter release as there was no detectable change in spontaneous e.j.p. amplitudes. In the presence of phentolamine, application of the adenosine uptake inhibitor, S‐(p‐nitrobenzyl)‐6‐thioinosine (0.1 μ M ), had no effect on e.j.p. amplitudes. The phosphodiesterase inhibitor, 3‐isobutyl‐1‐methylxanthine (100 μ M ), significantly increased the amplitudes of all e.j.ps evoked during trains of 20 stimuli at 1 Hz, both in the presence and in the absence of phentolamine (1 μ M ). These results suggest that endogenous adenosine modulates neurotransmitter release by an action at prejunctional A 1 adenosine receptors only when α 2 ‐adrenoceptors are blocked.British Journal of Pharmacology (1999) 126 , 1761–1768; doi: 10.1038/sj.bjp.0702514