Lee Tae-Seong, Kaku Toshihiko, Takebayashi Satoshi, Uchino Tomoko, Miyamoto Shinji, Hadama Tetsuo, Perez-Reyes Edward, Ono Katsushige
Department of Cardiovascular Science, Oita University School of Medicine, Oita, Japan.
Pharmacology. 2006;78(1):11-20. doi: 10.1159/000094900. Epub 2006 Aug 7.
We compared detailed efficacy of efonidipine and nifedipine, dihydropyridine analogues, and mibefradil using recombinant T- and L-type Ca2+ channels expressed separately in mammalian cells. All these Ca2+ channel antagonists blocked T-type Ca2+ channel currents (I(Ca(T))) with distinct blocking manners: I(Ca(T)) was blocked mainly by a tonic manner by nifedipine, by a use-dependent manner by mibefradil, and by a combination of both manners by efonidipine. IC50s of these Ca2+ channel antagonists to I(Ca(T)) and L-type Ca2+ channel current (I(Ca(L))) were 1.2 micromol/l and 0.14 nmol/l for nifedipine; 0.87 and 1.4 micromol/l for mibefradil, and 0.35 micromol/l and 1.8 nmol/l for efonidipine, respectively. Efonidipine, a dihydropyridine analogue, showed high affinity to T-type Ca2+ channel.
我们使用在哺乳动物细胞中分别表达的重组T型和L型Ca2+通道，比较了二氢吡啶类似物依福地平、硝苯地平和米贝地尔的详细疗效。所有这些Ca2+通道拮抗剂均以不同的阻断方式阻断T型Ca2+通道电流（I(Ca(T))）：硝苯地平主要以持续性方式阻断I(Ca(T))，米贝地尔以使用依赖性方式阻断，依福地平则以两种方式的组合阻断。这些Ca2+通道拮抗剂对I(Ca(T))和L型Ca2+通道电流（I(Ca(L))）的IC50分别为：硝苯地平为1.2 μmol/L和0.14 nmol/L；米贝地尔为0.87和1.4 μmol/L；依福地平为0.35 μmol/L和1.8 nmol/L。二氢吡啶类似物依福地平对T型Ca2+通道显示出高亲和力。
