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- W2040579784 abstract "The inhibitory effects of the nonpeptide angiotensin II (AII) receptor antagonist losartan and its active metabolite, E-3174, on bovine brain calcium/calmodulin-dependent 3':5'-cyclic nucleotide phosphodiesterase (cAMP PDE) were investigated. Losartan and E-3174 inhibited cAMP PDE activity competitively with an apparent Ki of 18.7 +/- 2 microM (N = 3) and 70.4 +/- 8 microM (N = 3) with respect to cAMP, respectively. With 1.2 mM cAMP as a substrate, cAMP PDE activities were inhibited by losartan and E-3174 in a concentration-dependent manner. The concentrations of losartan and E-3174 required to obtain 50% inhibition of the enzyme activity (IC50) were estimated to be 38.9 +/- 7 microM (N = 3) and 139.3 +/- 39 microM (N = 3), respectively. These results show that losartan is about four times more potent than E-3174 in inhibiting the enzyme. The Hill coefficient of -1.0 +/- -0.04 (N = 3) for losartan and -1.1 +/- -0.14 (N = 3) for E-3174 was obtained, indicating that one inhibitor binding site is available on cAMP PDE. This study demonstrated that losartan and E-3174 exert additional inhibitory action on cAMP PDE besides AII receptor antagonism." @default.
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- W2040579784 date "1994-07-01" @default.
- W2040579784 modified "2023-09-25" @default.
- W2040579784 title "Inhibitory effect of the nonpeptide angiotensin II receptor antagonist losartan and its active metabolite, E-3174, on cAMP phosphodiesterase: additional action of the antagonists" @default.
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- W2040579784 doi "https://doi.org/10.1016/0006-2952(94)90241-0" @default.
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