Villagrasa V, Ortiz J L, Sarriá B, Cejalvo D, Cortijo J, Morcillo E J
Departament de Farmacología, Universitat de València, Spain.
Methods Find Exp Clin Pharmacol. 1993 Jun;15(5):273-9.
CaCl2 (0.1-25 mM, in K(+)-depolarized tissues), KCl (10-112 mM) and acetylcholine (1 nM-1 mM) produced concentration-dependent contractions of rat isolated fundus. Nifedipine (0.01-500 mcM), diltiazem (0.01-100 mcM) and flunarizine (10-500 mcM) each produced a concentration-related inhibition of the log concentration-effect curve for CaCl2. The rank order of potencies of these antagonists, measured as the IC50 against Ca2+ (25 mM)-induced contraction of depolarized fundus, was nifedipine (1.9 mcM) = diltiazem (2.5 mcM) >> flunarizine (660 mcM). Diltiazem depressed KCl-induced contraction with an effectiveness and potency similar to that displayed against CaCl2 but nifedipine and flunarizine were less effective against contractions to KCl compared to CaCl2. Flunarizine (500 mc), but not the other antagonists tested, depressed Ca2+ (20 mc)-evoked contraction of skinned rat fundus preparations. It is concluded that distinct differences exist between the Ca2+ channel antagonists examined. The action of nifedipine and diltiazem is restricted to the plasmalemma, whereas flunarizine also acts on the intracellular contractile apparatus.
氯化钙（0.1 - 25 mM，在钾离子去极化组织中）、氯化钾（10 - 112 mM）和乙酰胆碱（1 nM - 1 mM）可使大鼠离体胃底产生浓度依赖性收缩。硝苯地平（0.01 - 500 μM）、地尔硫䓬（0.01 - 100 μM）和氟桂利嗪（10 - 500 μM）均可对氯化钙的对数浓度 - 效应曲线产生浓度相关的抑制作用。这些拮抗剂的效价顺序（以针对25 mM钙离子诱导的去极化胃底收缩的IC50衡量）为硝苯地平（1.9 μM）=地尔硫䓬（2.5 μM）>>氟桂利嗪（660 μM）。地尔硫䓬抑制氯化钾诱导的收缩的有效性和效价与抑制氯化钙诱导的收缩相似，但与氯化钙相比，硝苯地平和氟桂利嗪对氯化钾诱导的收缩作用较弱。氟桂利嗪（500 μM），而非其他受试拮抗剂，可抑制钙离子（20 μM）诱发的大鼠胃底皮肤制备物的收缩。结论是，所检测的钙离子通道拮抗剂之间存在明显差异。硝苯地平和地尔硫䓬的作用局限于质膜，而氟桂利嗪还作用于细胞内收缩装置。
