Potentiation of the relaxing action of isoproterenol by forskolin in rabbit aortic rings: the involvement of beta 2-adrenoceptors.
1. Forskolin, an activator of adenylate cyclase, potentiated the relaxing response to isoproterenol in rabbit aortic rings precontracted by phenylephrine (PE). 2. The potentiating effect of forskolin was inhibited by propranolol, a beta-adrenoceptor inhibitor, but not by methylene blue, a guanylate cyclase inhibitor. 3. The relaxing response to terbutaline, a beta 2-adrenoceptor agonist, but not lower concentrations of dobutamine, a beta 1-adrenoceptor agonist, also was potentiated by forskolin. Forskolin, however, potentiated the relaxing response to high concentrations of dobutamine, which activates both beta 1- and beta 2-adrenoceptors. 4. Yohimbine, an alpha 2-adrenoceptor inhibitor, glyburide, an ATP-sensitive K+ channel inhibitor, iberiotoxin, a Ca(2+)-activated K+ channel inhibitor, or endothelium-removal failed to affect the potentiating effect of forskolin. 5. Dibutyryl cyclic AMP (cAmp) also potentiated the relaxing response to terbutaline. 6. These results suggest that in rabbit aortic rings forskolin causes the apparent potentiation of isoproterenol-induced relaxation by mainly affecting the relaxing response due to the activation of beta 2-adrenoceptors by the forskolin-induced increase in the level of cAMP.
Satake
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N
Department of Pharmacology, University of Hawaii, School of Medicine, Honolulu 96822, USA.
Shibata
S
S
D000262:Adenylyl Cyclases / Q000378:metabolism*; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology*; D004280:Dobutamine / Q000494:pharmacology; D004357:Drug Synergism; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D013726:Terbutaline / Q000494:pharmacology
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D005576:Colforsin; D004280:Dobutamine; D003994:Bucladesine; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D013726:Terbutaline