Identification of R(-)-isomer of efonidipine as a selective blocker of T-type Ca2+ channels
Identification of R(-)-isomer of efonidipine as a selective blocker of T-type Ca2+ channels
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DOI：
10.1038/sj.bjp.0705944
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发表时间：
2004-12-01
影响因子：
7.3
通讯作者：
Nukada, T
中科院分区：
文献类型：
--
作者：
Furukawa, T;Miura, R;Nukada, T
1二氢吡啶钙拮抗剂的衍生物依曲地平对L和T型钙通道均有阻断作用。然而，尚不清楚伊福地平是否影响其他电压依赖性钙通道亚型，如N-、P/Q-和R-型，以及非诺地平的光学异构体在阻断这些钙通道方面是否具有不同的选择性，包括L和T-型。2.为了解决这些问题，我们在非洲爪哇卵母细胞和幼鼠肾细胞(BHK tk-ts13)的表达系统中，从电生理的角度观察了非诺地平及其R(-)和S(+)异构体对这些钙通道亚型的影响。4 S(+)-非那地平异构体对L和T-通道的选择性阻断作用重现。5相反，R(-)-非那地平异构体优先阻断T-通道。6非那地平及其对映体的阻断作用依赖于保持电位。7这些结果表明，非那地平的R(-)-异构体是T型钙通道的特异性阻滞剂。
1 Efonidipine, a derivative of dihydropyridine Ca2+ antagonist, is known to block both L- and T-type Ca2+ channels. It remains to be clarified, however, whether efonidipine affects other voltage-dependent Ca2+ channel subtypes such as N-, P/Q- and R-types, and whether the optical isomers of efonidipine have different selectivities in blocking these Ca2+ channels, including L- and T-types.2 To address these issues, the effects of efonidipine and its R(-)- and S(+)- isomers on these Ca2+ channel subtypes were examined electrophysiologically in the expression systems using Xenopus oocytes and baby hamster kidney cells (BHK tk-ts13).3 Efonidipine, a mixture of R(-)- and S(+)-isomers, exerted blocking actions on L- and T-types, but no effects on N-, P/Q- and R-type Ca2+ channels.4 The selective blocking actions on L- and T-type channels were reproduced by the S(+)-efonidipine isomer.5 By contrast, the R(-)-efonidipine isomer preferentially blocked T-type channels.6 The blocking actions of efonidipine and its enantiomers were dependent on holding potentials.7 These findings indicate that the R(-)-isomer of efonidipine is a specific blocker of the T-type Ca2+ channel.