Binding properties of a novel calcium channel activating dihydropyridine in monolayer cultures of beating myocytes

FEBS Letters

Bellemann, Peter¹ 

[1] Research Center, Bayer AG, PO Box 10 17 09, D-5600 Wuppertal-1, FRG

关键词: Dihydropyridine;    Ca2+-channel activation;    [3H]BAY K 8644;    Cultured myocardial cell;    [3H]Nimodipine;    Radioligand binding;    BBS;    balanced salt solution;    DMEM;    Dulbecco's modified Eagle's medium;    Hepes;    N-2-hydroxyethylpiperazine N′-2-ethanesulfonic acid;    BAY K 8644;    methyl 1;    4-dihydro-2;    6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine-5-carboxylate;   

DOI  :  10.1016/0014-5793(84)80838-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Binding characteristics of [³H]BAY K 8644, a new class of pharmacologically potent compounds, the calcium channel activating dihydropyridines (DHP), were demonstrated in cultured myocardial cells. [³H]BAY K 8644 exhibited reversible and saturable binding to myocytes, and specific binding was Ca²⁺-dependent. The equilibrium dissociation constant, K _d, was 35.2 nM, and maximal binding capacity, B _max, was 1.07 pmol/mg protein. Binding of the ³H-ligand was highly specific for various potently displacing DHP derivatives (either the calcium channel activating BAY K 8644, or the Ca²⁺ entry blockers of the nifedipine type) with inhibition constants (K _i values) in the nanomolar range. BAY K 8644, on the other hand, showed very low affinity to other receptors tested in brain and heart membranes. Displacement potency of BAY K 8644 correlated well with data of the functional pharmacology; e.g., the enhanced myocardial contractility. Results from competition studies using [³H]BAY K 8644 and [³H]nimodipine support the conclusion that both the channel activating and inhibiting DHP structures interact with the same specific receptor site that might be associated with the putative Ca²⁺-channel.

【 授权许可】

Unknown