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- W2017883957 abstract "The interaction of verapamil and other phenylalkylamine calcium channelblockers with the 1,4-dihydropyridine receptor was examined. Studies characterizing the interaction and relationship between calcium channel blocking potency and binding affinity were performed in rat myocardium. The 1,4-dihydropyridines, nifedipine and nitrendipine, interacted competitively. The apparent Kd and Bmax of nitrendipine were 270±140 pm and 390±76 fmol/mg protein, respectively. In contrast, the interaction of the phenylalkylamines with the 1,4-dihydropyridine receptor was not competitive. At a 3H-nitrendipine concentration of 0.12 nm, verapamil displaced only 60% of specifically bound radioactivity and progressively less as the concentration of 3H-nitrendipine increased. Kinetic data indicated that the interaction of both D600 and verapamil with the 1,4-dihydropyridine receptor was not cooperative. At infinite dilution the dissociation rate constant (k−1) was not altered in the presence of 10−5 m D600. We examined the hypothesis that 3H-nitrendipine interacts at several sites with similar affinities and that the phenylalkylamines interact at one of these sites. Although D600 could not further displace 3H-nitrendipine in the presence of a maximally displacing concentration of nifedipine (10−6 m), nifedipine could further displace 3H-nitrendipine in the presence of a maximally displacing concentration of D600 (10−5 m). These results are consistent with competitive interactions at multiple sites but do not explain the diminished ability of the phenylalkylamines to displace progressively less radioactivity at increasing 3H-nitrendipine concentrations. No relationship between binding affinity and pharmacologic potency of the phenylalkylamines was found suggesting that the interaction of the phenylalkylamines with the 1,4-dihydropyridine receptor is not responsible for their calcium channel blocking effects." @default.
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- W2017883957 date "1990-09-01" @default.
- W2017883957 modified "2023-09-25" @default.
- W2017883957 title "The molecular and pharmacological basis for using calcium antagonists in hypertension" @default.
- W2017883957 doi "https://doi.org/10.1016/s1043-6618(09)80256-9" @default.
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