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 rat mesenteric artery and rabbit ear artery were compared with those of a number of purinoceptor agonists. 2. In the rat mesenteric artery, the P1 receptor agonists 2-chloroadenosine (2CA) and 5'-N-ethylcarboxamidoadenosine (NECA) and the P2 purinoceptor agonists beta,gamma-methylene ATP (betagammamATP) and 2-methylthio ATP (2mSATP) significantly inhibited the release of NA in a xanthine-sensitive manner. HAK2701 did not significantly inhibit the release of NA, the relative order of potency being betagammamATP > NECA > 2CA > 2mSATP >> HAK2701. 3. In the rabbit ear artery, both P1 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 > betagammamATP > 2CA > 2mSATP > NECA. 4. These findings suggest that HAK2701 may be a potent and selective agonist for facilitatory prejunctional purinoceptors, but not for inhibitory purinoceptors, on adrenergic nerve terminals.
Departments of Pharmacology, Faculty of Pharmaceutical Science, Mukogawa Women's University, Nishinomiya, Japan. kazumasa@mwu.mukogawa-u.ac.jp
K
K
Shinozuka
R
R
Ishii-Nozawa
K
K
Takeuchi
N
N
Minakawa
A
A
Matsuda
H
H
Nakata
M
M
Kunitomo
D015762:2-Chloroadenosine / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000320:Adrenergic Fibers / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D004423:Ear / Q000098:blood supply / Q000502:physiology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D058906:Purinergic P1 Receptor Agonists; D058910:Purinergic P2 Receptor Agonists; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D013873:Thionucleotides / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
C113340:9-(6,7-dideoxyhept-5-ynofuranosyl)adenine; C092578:FPL 66301; D058906:Purinergic P1 Receptor Agonists; D058910:Purinergic P2 Receptor Agonists; D018047:Receptors, Purinergic P1; D018048:Receptors, Purinergic P2; D013873:Thionucleotides; D014665:Vasodilator Agents; D015762:2-Chloroadenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D000255:Adenosine Triphosphate; D000241:Adenosine; D009638:Norepinephrine; C008501:2-methylthio-ATP