MECHANISMS OF THE CONTRACTILE EFFECTS OF FLOSEQUINOXAN

In guinea-pig papillary muscles the positive inotropic effect of flose quinoxan (BTS) starting at 100 mu mol/l amounted to 287.6 +/- 34.2% at 300 mu mol/l without any effects on time to peak tension (103.9 +/- 2 %) and relaxation time (107.1 +/- 6.7% of predrug value, respectively) . 10 mu mol/l carbachol attenuated the positive inotropic effect of 30 0 mu mol/l to 166.5 +/- 11.6% (n = 10). The phosphorylation state of t he inhibitory subunit of troponin (TnI) and phospholamban (PLB) in [P- 32]-labeled guinea-pig ventricular myocytes was increased starting at 100 mu mol/l amounting to 142.5 +/- 12.6% and 130.9 +/- 2.2% at 300 mu mol/l, respectively (n = 5). Furthermore, BTS (300 mu mol/l) decrease d phosphorylase phosphatase activity by 23.1%. It is concluded that th e contractile effects of BTS are accompanied by enhanced phosphorylati on of regulatory proteins which could in part be due to inhibition of phosphorylase phosphatase activity.