An explanation of bell-shaped, dose-positive inotropic effect curves for denopamine in canine right ventricular muscle

Hitoshi Yokoyama, Kuniaki Ishii, Teruyuki Yanagisawa, Norio Taira

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

We investigated mechanisms by which denopamine produces bell-shaped, cumulative concentration-response curves for positive inotropic effect in canine right ventricular muscle. As in our previous study, the curves ascended at 10-8 to 10-6 M, reached a maximum at 3 × 10-6 to 10-5 M, and descended at higher concentrations. The ascending limb gave 6.58 ± 0.21 for the pD2 value. Denopamine, when administered cumulatively up to 3 × 10-5 to 3 × 10-4 M, caused rightward shifts of concentration-response curves for the positive inotropic effect of isoproterenol. Application of a two-component fitting model to the concentration-response curves for isoproterenol in the presence of denopamine yielded two pA2 values of denopamine; 6.59 ± 0.19 for the high- and 5.05 ± 0.21 for the low-affinity state of 13, receptors. The bell-shaped curves for denopamine were successfully computer-simulated with the following assumptions. (a) Denopamine produces a positive inotropic effect by binding to the high-affinity state of 13, receptors with an apparent dissociation constant of 10-6.59 M. (b) The fraction of the high-affinity state decreases as denopamine binds to the low-affinity state with an apparent dissociation constant of 10-5.05 M. Cyclic AMP levels were changed by denopamine, isoproterenol, and a combination of both, roughly in a parallel way to changes in positive inotropic effect.

Original languageEnglish
Pages (from-to)570-576
Number of pages7
JournalJournal of cardiovascular pharmacology
Volume14
Issue number4
DOIs
Publication statusPublished - 1989 Oct

Keywords

  • Cardiotonic agent
  • Cyclic AMP
  • Denopamine
  • β Agonist
  • β Receptors

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'An explanation of bell-shaped, dose-positive inotropic effect curves for denopamine in canine right ventricular muscle'. Together they form a unique fingerprint.

Cite this