Evidence for ATP as a cotransmitter in dog mesenteric artery

Contractile responses of the dog mesenteric artery were obtained (after removal of endothelium) to transmural stimulation of the perivascular nerves and to exogenous application of ATP, noradrenaline, dopamine, 5-hydroxy-tryptamine and high potassium solution. The alpha-adrenoceptor antagonists prazosin and phentolamine preferentially reduced the response to noradrenaline and the secondary phase of the biphasic contractile response to nerve stimulation, whilst the addition of alpha, beta-methylene-ATP, which selectively desensitizes P2-purinoceptors, reduced only the contractions to ATP and the portion of the nerve-mediated response which was resistant to the alpha-adrenoceptor antagonists. The responses to nerve stimulation were reduced by the selective P1-purinoceptor agonist 2-chloroadenosine, and its effect was reversed by the P1-purinoceptor antagonist 8-phenyltheophylline. These results suggest that in dog mesenteric artery part of the response to sympathetic nerve stimulation is mediated by ATP acting on P1-purinoceptors on the arterial smooth muscle, and that P1-purinoceptors on the sympathetic nerve terminal can inhibit release of the neurotransmitters.