Studies of drug influence on ATPase activity in animal tissues: Part III. Effect of SIN-1 A, nitroglycerin, trimetazidine, trifluoperazine, ouabain and N-ethylmaleimide on activity of Ca(Mg)-ATPase in microsomal fraction on guinea-pig aorta and ventricular muscle.

Abstract

It was reported that SIN-1 A (active metabolite of molsidomin, 0.1 to 1.0 mM) and nitroglycerin (0.2 mM) increase Ca(Mg)-ATPase activity in microsomal fraction of guinea-pig aorta and ventricular muscle (in the last meeting, Syoji et al. 1982). The increase of the activity induced by the drugs became more remarkable with reduction of the added Ca ion from 20.0 to 2.5 mM. In the present work, it is reported that trimetazidine (0.3 mM), ouabain (0.25 mM), N-ethylmaleimide (NEM, 0.1 mM), verapamil (0.1 mM) and trifluoperazine (TFP, 0.02 mM) all have no significant influence on the Ca(Mg)-ATPase activity. However, the increase of the Ca(Mg)-ATPase activity induced by SIN-1 A (1.0 mM) was counteracted by the simultaneous presence of TFP (0.02 mM), but was not influenced by ouabain (0.25 mM), NEM (0.1 mM) or verapamil (0.1 mM). In the experiment, the reaction mixture for the ATPase consisted (mM) of MgCl2, 0.5; Cad-, 2.5; NaCl, 75.0; ATP, 5.0; tris-acetate, 50.0; and the drug tested. Next, the effect of nitroglycerin and SIN-1 A on contractile force of the spirally cut preparation of guinea-pig thoracic aorta was examined in Krebs-Ringer’s solution at a temperature of 36°C. The contractile force of the preparation which was previously increased by prostaglandin F2α (0.5 μM) was decreased by nitroglycerin (0.01 to 1.0 μM) or SIN-1A (0.012αto 1.0 μM) in each concentration-dependent manner.