Differential coupling to positive inotropic responses of cyclic AMP produced by stimulation of beta 1- and beta 2-adrenergic receptors.
In canine right ventricular muscle, isoproterenol, a nonselective beta-agonist, and T-1583, a selective beta 1-agonist, produced positive inotropic effects (PIE) as full agonists. Their PIEs were antagonized by atenolol, a selective beta 1-antagonist, (pA2 = 7.71 for isoproterenol and pA2 = 7.82 for T-1583). The PIE of T-1583 was also antagonized by practolol, a selective beta 1-antagonist (pA2 = 6.55). Procaterol known as a selective beta 2-agonist gave a biphasic concentration-response curve with a maximum that was approximately half those of isoproterenol and T-1583. The PIE of procaterol at low concentrations (pD2 = 7.93), which maximum was approximately 10% of the maximum of isoproterenol, was antagonized by ICI 118,551, a selective beta 2-antagonist (ICI; pA2 = 8.84) and that at high concentrations (pD2 = 5.12) by atenolol (pA2 = 7.56). Increases in cyclic AMP content produced by isoproterenol were reduced greatly by atenolol and slightly by ICI, whereas those produced by T-1583, which were smaller than those by isoproterenol, were abolished by atenolol but not changed by ICI. Procaterol (10(-7) M) produced an increase in cyclic AMP, which was abolished by ICI but not changed by atenolol, to almost the same extent as procaterol (10(-5) M) did, which was abolished by atenolol and slightly reduced by ICI. These results indicate that increased cyclic AMP through beta 1- but not beta 2-receptors couples well to PIE.
Yanagisawa
T
T
Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
Ishii
K
K
Hashimoto
H
H
Taira
N
N
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002395:Catecholamines / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D004285:Dogs; D004983:Ethanolamines / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D017265:Procaterol; D011412:Propanolamines / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013268:Stimulation, Chemical
D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D004983:Ethanolamines; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C059333:T 1583; C026777:ICI 118551; D000242:Cyclic AMP; D007545:Isoproterenol; D017265:Procaterol