The P1-purinoceptors that mediate the prejunctional inhibitory effect of adenosine on capsaicin-sensitive nonadrenergic noncholinergic neurotransmission in the rat mesenteric arterial bed are of the A1 subtype.

It has been shown that capsaicin-sensitive sensory-motor nerves contribute to the control of peripheral vascular resistance by releasing the potent vasodilator calcitonin gene-related peptide. The purpose of the present study was to characterize the P1-purinoceptor subtype that modulates capsaicin-sensitive non-adrenergic noncholinergic (NANC) neurotransmission in the rat mesenteric arterial bed. Analogs of adenosine, selective for the adenosine receptor subtypes A1 or A2, were evaluated on the vasodilator response to electrical stimulation of capsaicin-sensitive sensory-motor nerves. The order of potency of adenosine receptor agonists to inhibit the NANC neurotransmission was: the selective adenosine A1 receptor agonist N6cyclopentyl-adenosine > or = R-phenylisopropyladenosine > 5'N-ethylcarboxamide adenosine > or = 2-chloroadenosine > or = S-phenylisopropyladenosine. The A2-selective agonist CGS 21680 was devoid of any effect on NANC neurotransmission. In addition, the selective A1 receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine inhibited the effect of adenosine. None of the agonists tested showed direct action on the tone of the mesenteric vasculature. Neither N6cyclopentyladenosine nor adenosine modified the vasodilator response to exogenous calcitonin gene-related peptide. Moreover, adenosine failed to affect the vasodilator response to capsaicin. In conclusion, these results indicate that adenosine and its analogs inhibit NANC neurotransmission via prejunctional P1-purinoceptors of the A1 subtype. The inhibitory action of adenosine appears to be selective for the release of transmitters during electrical activation of sensory-motor nerve endings, adenosine being inactive on capsaicin-induced vasodilatation.