Interaction of the calcium channel activating 3H-BAY K 8644 and inhibiting 3H-verapamil with specific receptor sites on cultured beating myocardial cells.
Interaction of the calcium channel activating 3H-BAY K 8644 and inhibiting 3H-verapamil with specific receptor sites on cultured beating myocardial cells.
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钙通道激活 3H-BAY K 8644 和抑制 3H-维拉帕米与培养的跳动心肌细胞上特定受体位点的相互作用。
DOI：
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
P. Bellemann
中科院分区：
文献类型：
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作者：
P. Bellemann
在跳动的心肌细胞单层培养中，证实了激活二氢吡啶(DHP)的钙通道H-Bay K 8644和抑制~3H-维拉帕米的钙通道的结合特性。~3H-Bay K 8644的特异性结合依赖于细胞外钙离子的存在，亲和力受钙离子的调节，但Hill系数不受影响。BAY K 8644对静息和搏动心肌细胞的收缩有刺激作用。然而，与β-肾上腺素能受体激动剂相比，该化合物对培养的心肌细胞中cAMP和cGMP的细胞水平没有影响。钙通道激活剂Bay K 8644的二氢吡啶衍生物以及阻断钙离子内流的硝苯地平或尼莫地平类型的DHP与脑和心脏膜上的其他受体亲和力很低。~3H-Bay K 8644结合位点对各种取代DHP衍生物具有很高的特异性，并能区分光学异构体(立体选择性)和抑制常数(KI)在纳摩尔范围内。竞争曲线的不同形状也表明这些化合物与DHP受体的不同(亚)位点相互作用，这代表了调节跨膜钙电流的一个相互作用点。另一种与DHP受体明显不同的强效二苯基烷基胺的作用部位用~3H-维拉帕米进行了表征。培养心肌细胞的平衡解离常数Kd在16-25 nM之间，结合容量Bmax约为1.85pmol/mg蛋白质。不同的竞争模式表明有多个~3H-维拉帕米结合位点参与。结构不同的通道调节剂与位于钙通道内或附近的不同放射性标记的受体(亚)位置之间的相互关系可能是研究这些有效化合物作用性质的新途径。
Binding properties of the calcium channel activating dihydropyridine (DHP), H-BAY K 8644, and the inhibiting 3H-verapamil were demonstrated in monolayer cultures of beating cardiac cells. 3H-BAY K 8644 specific binding was dependent on the presence of extracellular calcium, the affinity was modulated by Ca2+, but Hill coefficients remained unaffected. BAY K 8644 stimulated myocardial contractility in resting and beating myocytes. In contrast to beta-adrenoceptor agonists, however, cellular levels of cyclic AMP and cyclic GMP in cultured myocytes remained unchanged by the compound. Dihydropyridine derivatives of both the calcium channel activating BAY K 8644 as well as the Ca2+ entry blocking DHPs of the nifedipine or nimodipine type yielded very low affinity to other receptors measured in brain and heart membranes. 3H-BAY K 8644 binding sites proved to be highly specific for various potently displacing DHP derivatives and discriminated between optical isomers (stereoselectivity) with inhibition constants (Ki) in the nanomolar range. The heterogeneous shapes of the competition curves also imply interactions of these compounds with different (sub-)sites of the DHP receptor that represents one locus of interaction in regulating transmembranal Ca2+ currents. The other specific site of action for the potent diphenylalkylamines, clearly different to the DHP receptor was characterized with 3H-verapamil. The equilibrium dissociation constant, Kd in cultured myocytes ranged between 16-25 nM, and binding capacity, Bmax amounted to about 1.85 pmol/mg of protein. The different mode of competitions indicates the involvement of more than one 3H-verapamil binding site. The interrelation of the structurally heterogeneous channel modulators with the differently radiolabelled receptor (sub-)sites located in or near by the calcium channel may represent new approaches in investigating the nature of action of these potent compounds.
Ca 拮抗剂对阻力血管中 Ca 通量的影响。
影响因子：
3
作者：
Cauvin,C;Saida,K;vanBreemen,C
通讯作者：
vanBreemen,C