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• W2048193769 abstract "The relative effects of felodipine, a dihydropyridine with purported calmodulin antagonistic properties, have been compared with the calmodulin inhibitor, W-7, for inhibition of Ca2+-dependent force development and direct inhibition of Ca2+-calmodulin mediated arterial myosin light chain phosphorylation and actin-myosin interactions. Felodipine (IC50 3 X 10(-9) M) was approximately 30 000 X more potent than W-7 (IC50 10(-4) M) and equipotent with another dihydropyridine, nitrendipine, in inhibiting isometric force development in K+-depolarized aortic smooth muscle strips. In contrast, W-7 (IC50 4 X 10(-5) M) was approximately 5 X more potent than felodipine (IC50 2 X 10(-4) M) in inhibiting Ca2+-dependent myosin light chain phosphorylation or superprecipitation of arterial actomyosin. Concentration-related inhibition of both parameters by W-7 was tightly coupled to concomitant inhibition of force development in intact smooth muscle. In contrast, inhibition of myosin light chain phosphorylation and superprecipitation by felodipine was only apparent at concentrations greater than or equal to 10(-5) M while maximal inhibition of force development occurred at a concentration as low as 10(-7) M. Inhibition of contractility by W-7 was minimal in paced rabbit atria, whereas inhibition by felodipine was similar to that seen with nitrendipine. These results suggest that the pharmacologically-relevant mechanism of Ca2+ antagonism in smooth muscle by felodipine is similar to nitrendipine (blockade of the Ca2+ entry channel) and does not involve direct inhibition of Ca2+-calmodulin stimulated myosin light chain phosphorylation and subsequent actin-myosin interactions." @default.
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• W2048193769 date "1984-07-01" @default.
• W2048193769 modified "2023-09-25" @default.
• W2048193769 title "Effects of felodipine, nitrendipine and W-7 on arterial myosin phosphorylation, actin-myosin interactions and contraction" @default.
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• W2048193769 doi "https://doi.org/10.1016/0014-2999(84)90561-2" @default.
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