Feoktistov I A, Baldenkov G N, Barannik I V, Cherviakov E B, Larionov N P
Biokhimiia. 1990 Apr;55(4):754-9.
The effects of Ca2+ antagonists (nicardipine, felodipine, nitrenedipine, isradipine, niphedipine, darodipine and riodipine) and Ca2+ agonists (BAY K8644 and CGP 28392), 1.4-dihydropyridine derivatives (1.2-DHP), on the calmodulin (CM)-dependent activation of cyclic nuxleotide phosphodiesterase (PDE) were studied. Both the blockers and activators of slow potential-dependent Ca2+ channels induced a un-competitive inhibition of the CM-dependent PDE activity. 1.4-DHP was found to replace the fluorescent probe, diS-C3-(5), from the Ca2(+)-dependent calmodulin-dye complex (K0.5 = 4-60 microM) but at concentrations below 100 microM had no effect on the Ca2(+)-dependent troponin C-dye complex. Darodipine (100 microM) did not interact with the proteins. The 1.4-DHP interaction with CM did not interfere with PDE activation. It is concluded that 1.4-DHP may affect Ca2+ dependent processes not only at the levels of activation or blocking of Ca2+ channels, but also through regulation of Ca2(+)-CM dependent enzymes.
研究了钙拮抗剂（尼卡地平、非洛地平、尼群地平、伊拉地平、硝苯地平、达罗地平及硫氮卓酮）和钙激动剂（BAY K8644及CGP 28392），即1,4 - 二氢吡啶衍生物（1,2 - DHP）对钙调蛋白（CM）依赖性环核苷酸磷酸二酯酶（PDE）激活的影响。慢电位依赖性钙通道的阻滞剂和激动剂均能引起对CM依赖性PDE活性的非竞争性抑制。发现1,4 - DHP能从钙依赖性钙调蛋白 - 染料复合物中取代荧光探针二硫氰基苯并噻唑（K0.5 = 4 - 60微摩尔），但在浓度低于100微摩尔时对钙依赖性肌钙蛋白C - 染料复合物无影响。达罗地平（100微摩尔）不与蛋白质相互作用。1,4 - DHP与CM的相互作用并不干扰PDE的激活。结论是，1,4 - DHP不仅可能在钙通道激活或阻断水平影响钙依赖性过程，还可能通过调节钙 - CM依赖性酶来发挥作用。
