Effects of a new 1,3-thiazole derivative ZSY-39 on force of contraction and cyclic AMP content in canine ventricular muscle.
A newly synthesized 1,3-thiazole derivative ZSY-39 increased the force of contraction in a concentration-dependent manner in association with elevation of tissue cyclic AMP levels in the isolated canine ventricular trabeculae electrically driven at 0.5 Hz at 37 degrees C. ZSY-39 shortened the duration of isometric contractions mainly by abbreviation of the relaxation time. The maximal response to and EC50 of ZSY-39 were 0.7 (isoproterenol = 1.0) and 4.6 x 10(-5) M. Bupranolol (3 x 10(-7) M) did not affect the positive inotropic effect of ZSY-39. The time course of increases in the force of contraction induced by ZSY-39 (10(-4) M) coincided with that of cyclic AMP accumulation. The concentration-response curve for the increase in the force of contraction produced by ZSY-39 was superimposable on that of the elevation of cyclic AMP levels. Carbachol (3 x 10(-6) M) shifted the concentration-response curve for the increase in force by ZSY-39 to the right and downward, and decreased the accumulation of cyclic AMP induced by ZSY-39 (10(-4) M). ZSY-39 (10(-5) M) enhanced significantly the positive inotropic effect of isoproterenol. The relationship between the force of contraction and cyclic AMP levels after the administration of ZSY-39 was not modified by the addition of carbachol or isoproterenol. These findings indicate that cyclic AMP plays an important role in the positive inotropic effect of ZSY-39 on canine ventricular muscle.
Endoh
M
M
Department of Pharmacology, Yamagata University School of Medicine, Japan.
Satoh
H
H
Norota
I
I
Hirano
K
K
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D000242:Cyclic AMP / Q000032:analysis*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006352:Heart Ventricles; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000737:chemistry*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
D002316:Cardiotonic Agents; D010726:Phosphodiesterase Inhibitors; D011725:Pyridines; D013844:Thiazoles; C053030:4-methyl-5-(4-pyridinyl)thiazole-2-carboxamide; D002217:Carbachol; D000242:Cyclic AMP; D007545:Isoproterenol