Effect of 9-(6,7-dideoxy-beta-D-allo-hept-5-ynofuranosyl)adenine on noradrenaline release from vascular sympathetic nerves

1. The effects of 9-(6,7-dideoxy-beta -D-allo-hept-5-ynofuranosyl)- adenine (HAK2701), a selective and potent ligand for P3 receptor-like protein, on the release of endogenous noradrenaline (NA) from electrically stimulated r at mesenteric artery and rabbit ear artery were compared with those of a nu mber of purinoceptor agonists. 2. In the fat mesenteric artery, the pi receptor agonists 2-chloroadenosine (2CA) and 5'-N-ethylcarboxamidoadenosine (NECA) and the P2 purinoceptor ag onists beta,gamma -methylene ATP (beta gamma mATP) and 2-methylthio ATP (2m SATP) significantly inhibited the release of NA in a xanthine-sensitive man ner. HAK2701 did not significantly inhibit the release of NA, the relative order of potency being beta gamma mATP > NECA > 2CA > 2mSATP >> HAK2701. 3. In the rabbit ear artery, both pi and P2 receptor agonists significantly facilitated the release of NA in a xanthine-sensitive manner. HAK2701 also significantly facilitated the release of NA, the relative order of potency being HAK2701 > beta gamma mATP > 2CA > 2mSATP > NECA. 4. These findings suggest that HAK2701 may be a potent and selective agonis t for facilitatory prejunctional purinoceptors, but not for inhibitory puri noceptors, on adrenergic nerve terminals.