Selective β1-receptor full agonists, T-0509 and T-1583, increase the force monophasically and cyclic AMP biphasically in canine ventricular muscle

Hideo Kurosawa, Eisaku Satoh, Teruyuki Yanagisawa, Norio Taira

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

In canine right ventricular muscle, we investigated the mechanism of action of the positive inotropic effects of T-0509 and T-1583, derivatives of denopamine, a new selective β1-partial agonist. T-1583 has already been characterized as a selective β1 full agonist (pD2 = 7.39). T-0509 also behaved as a full agonist (pD2 = 8.27) and its positive inotropic effect was antagonized competitively by atenolol (pA2 = 7.53) and non-competitively by carbachol, and potentiated by 3-isobutyl-l-methyl-xanthine. With increasing concentrations of T-0509 (10-9 to 10-7 M) and T-1583 (10-8 to 10-6 M), cyclic AMP increased and increases reached plateaus 40% above the baseline levels with 10-7 M T-0509 and 10-6 M T-1583, at which their positive inotropic effects reached maxima. However, with further increasing concentrations, cyclic AMP again started to increase and increases amounted to 120% above the baseline levels with 10-5 M T-0509 and with 10-4 M T-1583. These results suggest the following: Like denopamine, the selective β1 full agonists, T-0509 and T-1583, at lower concentrations produce positive inotropic effects accompanied by only a small increase in cyclic AMP via stimulation of high-affinity β1-receptors. In higher concentrations, unlike denopamine, the two full agonists produce large increases in cyclic AMP loosely coupled to positive inotropy via stimulation of low-affinity β1-receptors.

Original languageEnglish
Pages (from-to)646-653
Number of pages8
JournalJournal of cardiovascular pharmacology
Volume16
Issue number4
DOIs
Publication statusPublished - 1990 Oct

Keywords

  • Cyclic AMP
  • Positive inotropic effect
  • T-0509
  • T-1583
  • β-Receptors

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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