Differential coupling to positive inotropic responses of cyclic AMP produced by stimulation of β1- and β2-adrenergic receptors

T. Yanagisawa, K. Ishii, H. Hashimoto, N. Taira

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

In canine right ventricular muscle, isoproterenol, a nonselective β-agonist, and T-1583, a selective β1-agonist, produced positive inotropic effects (PIE) as full agonists. Their PIEs were antagonized by atenolol, a selective β1-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 β1-antagonist (pA2 = 6.55). Procaterol known as a selective β2-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 ~10% of the maximum of isoproterenol, was antagonized by ICI 118,551, a selective β2-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 β1- but not β2-receptors couples well to PIE.

Original languageEnglish
Pages (from-to)64-75
Number of pages12
JournalJournal of cardiovascular pharmacology
Volume13
Issue number1
Publication statusPublished - 1989

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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