Genistein potentiates the relaxation induced by beta1- and beta2-adrenoceptor activation in rat aortic rings.
In rat aortic rings, genistein, an inhibitor of tyrosine kinase, but not daidzein, an inactive analogue of genistein, potentiated the relaxation induced by isoproterenol. Atenolol, a beta1-adrenoceptor antagonist, or ICI-118,551, a beta2-adrenoceptor antagonist, inhibited the relaxation induced by isoproterenol. The potentiating effect of genistein on the relaxation induced by isoproterenol in the presence of ICI-118,551 was apparently greater than that in the presence of atenolol. In the presence of ICI-118,551, theophylline, an inhibitor of cyclic adenosine monophosphate (cAMP)-dependent phosphodiesterase (cAMP-PDE), markedly inhibited the potentiating effect of genistein on the isoproterenol-induced relaxation, whereas in the presence of atenolol, theophylline only partly inhibited the potentiating effect of genistein. The relaxation induced by forskolin, an activator of adenylyl cyclase, was potentiated by genistein or theophylline. In the presence of theophylline, the relaxation induced by forskolin was not further affected by genistein. Genistein also inhibited the activities of cAMP-PDE. In the presence of atenolol, but not ICI-118,551, iberiotoxin, an inhibitor of Ca-activated K channels, inhibited the relaxation induced by isoproterenol and the potentiating effect of genistein. In the presence of atenolol, quinacrine, an inhibitor of phospholipase A2, and metyrapone, an inhibitor of P-450 enzymes, but not alpha-naphthoflavone, an inhibitor of P-450 enzymes, indomethacin, a cyclooxygenase inhibitor, or AA861, a 5-lipoxygenase inhibitor, inhibited the potentiating effect of genistein. These results suggest that the potentiation of the beta1-adrenoceptor-induced relaxation by activation of genistein may mostly be due to inhibition of cAMP-PDE activities. In addition, the potentiation of the relaxation induced by activation of beta2-adrenoceptors by genistein may be related to the inhibition of arachidonic acid metabolism and cAMP-PDE activities.
Satake
N
N
Department of Pharmacology, University of Hawaii, School of Medicine, Honolulu 96822, USA.
Imanishi
M
M
Keto
Y
Y
Yamada
H
H
Ishikawa
M
M
Shibata
S
S
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019833:Genistein / Q000494:pharmacology*; D066298:In Vitro Techniques; D007529:Isoflavones / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011941:Receptors, Adrenergic / Q000145:classification / Q000187:drug effects*; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D007529:Isoflavones; D011941:Receptors, Adrenergic; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; C004742:daidzein; D019833:Genistein; D007545:Isoproterenol