Dissociation of cyclic AMP and contractile responses to isoprenaline: effects of a dihydropyridine derivative, nicardipine (YC-93), on canine ventricular muscle

Masao Endoh, Teruyuki Yanagisawa, Norio Taira

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Nicardipine (YC-93), a 1,4-dihydropyridine derivative, inhibited the cyclic AMP phosphodiesterase (PDE) activity of purified PDE in a cell-free preparation. Its inhibitory action on the purified PDE was about seven times that of papaverine. On the other hand, YC-93 did not affect the intracellular cyclic AMP level and the accumulation of cyclic AMP caused by isoprenaline in the isolated canine right ventricular myocardium. YC-93 caused a prominent negative inotropic action which developed gradually to reach a steady level 1 h after its administration. The potency of YC-93 to depress the force of contraction was one tenth that of D600. The dose-response curve for isoprenaline was shifted to the right and downward in the presence of YC-93 in a concentration-dependent manner, and the positive inotropic action of calcium was also inhibited markedly by YC-93. The depressant action of YC-93 on the positive inotropic actions of isoprenaline and calcium was more prominent than that of D600. Although YC-93 is a potent PDE inhibitor in the cell-free preparation, the PDE in the intact cell system may be not accessible to the drug. Thus, it is considered that YC-93 acted as a calcium antagonistic drug on the isolated canine ventricular myocardium, and thereby inhibited the positive inotropic action of isoprenaline without affecting the intracellular accumulation of cyclic AMP caused by isoprenaline.

Original languageEnglish
Pages (from-to)225-233
Number of pages9
JournalEuropean Journal of Pharmacology
Volume67
Issue number2-3
DOIs
Publication statusPublished - 1980 Jan 1

Keywords

  • Calcium
  • Cyclic AMP phosphodiesterase
  • Dihydropyridine derivative
  • Inotropic action
  • β-Adrenoceptor stimulation Ventricular contraction

ASJC Scopus subject areas

  • Pharmacology

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