Inhibition of turkey gizzard myosin light chain kinase activity by BAY K 8644.
BAY K 8644, a dihydropyridine with positive inotropic effects in smooth muscle, was found to inhibit calmodulin-dependent turkey gizzard myosin light chain kinase activity with an IC50 of 80 microM. In contrast, when myosin light chain kinase was rendered calmodulin-independent by limited proteolysis, drug inhibition was markedly diminished. BAY K 8644 inhibition was additive with that of the negative-inotropic dihydropyridine felodipine. These results indicate that the inotropic effects of dihydropyridines in smooth muscle are unrelated to their calmodulin-antagonistic properties.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D015736:Felodipine; D005895:Gizzard, Avian / Q000201:enzymology*; D066298:In Vitro Techniques; D009219:Myosin-Light-Chain Kinase; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009568:Nitrendipine; D047428:Protein Kinase Inhibitors; D014422:Turkeys / Q000378:metabolism*
D002121:Calcium Channel Blockers; D002147:Calmodulin; D047428:Protein Kinase Inhibitors; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009568:Nitrendipine; D009219:Myosin-Light-Chain Kinase; D009543:Nifedipine; D015736:Felodipine