TY - JOUR T1 - Selectivities of Dihydropyridine Derivatives in Blocking Ca<sup>2+</sup> Channel Subtypes Expressed in <em>Xenopus</em>Oocytes JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 464 LP - 473 VL - 291 IS - 2 AU - Taiji Furukawa AU - Takeshi Yamakawa AU - Takayuki Midera AU - Toshio Sagawa AU - Yasuo Mori AU - Toshihide Nukada Y1 - 1999/11/01 UR - http://jpet.aspetjournals.org/content/291/2/464.abstract N2 - Some dihydropyridines (DHPs), such as amlodipine and cilnidipine, have been shown to block not only L-type but also N-type Ca2+channels; therefore, DHPs are no longer considered as L-type-specific Ca2+ channel blockers. However, selectivity of DHPs for Ca2+ channel subtypes including N-, P/Q-, and R-types are poorly understood. To address this issue at the molecular level, blocking effects of 10 DHPs (nifedipine, nilvadipine, barnidipine, nimodipine, nitrendipine, amlodipine, nicardipine, benidipine, felodipine, and cilnidipine) on four subtypes of Ca2+channels (L-, N-, P/Q-, and R-types) were investigated in theXenopus oocyte expression system with the use of the two-microelectrode voltage-clamp technique. L-type Ca2+channels expressed as α1Cα2β1a combination were profoundly blocked by all DHPs examined, whereas blocking actions of these DHPs on R-type (α1Eα2β1a) channels were equally weak. In contrast, 5 of the 10 DHPs (amlodipine, benidipine, cilnidipine, nicardipine, and barnidipine) significantly blocked N-type (α1Bα2β1a) and P/Q-type (α1Aα2β1a) Ca2+channels. These selectivities of DHPs in blocking Ca2+channel subtypes would provide useful pharmacological and clinical information on the mode of action of the drugs including side effects and adverse effects. The American Society for Pharmacology and Experimental Therapeutics ER -