Characterization of prejunctional purinoceptors inhibiting noradrenaline release in rat mesenteric arteries.

The effects of purinoceptor agonists on noradrenaline NA release by electrical stimulation in rat mesenteric arteries were examined to clarify the pharmacological properties of prejunctional purinoceptors on adrenergic nerves. Adenosine and the other P1-receptor agonists, 5'-(N-ethylcarboxamido) adenosine and 2-chloroadenosine, significantly inhibited the release of NA. Also beta,gamma-methylene ATP and 2-methylthio ATP, P2-receptor agonists, significantly inhibited NA releases. The inhibitory effect of adenosine was significantly reduced by adenosine deaminase, but those of beta,gamma-methylene ATP and 2-methylthio ATP were not affected. This suggests that the inhibitory effects of P2-receptor agonists are not due to conversion into adenosine. 1,3-Dipropyl-8-cyclopentylxanthine (DPCPX), a P1 (A1)-receptor antagonist, significantly reduced the inhibitory effects of not only the P1- but also P2-receptor agonists. Therefore, DPCPX appears to act on both prejunctional P1- and P2-receptor as an antagonist. Pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), a P2-receptor antagonist, significantly reduced the inhibitory effects of the P2-receptor agonists, but not those of the P1-receptor agonists. From these findings in the rat mesenteric artery, the P1-receptor agonist-induced inhibition of NA-release appears to be mediated via a well-known prejunctional P1-receptor of the A1-subtype, but the P2-receptor agonist-induced inhibition appears to be mediated via an unidentified purinoceptor that is blocked not only by P2-receptor antagonists but also by P1-receptor antagonists.