Martí-Cabrera M, Llopis P, Abengochea A, Ortiz J L, Climent V J, Cortijo J, Morcillo E J
Departament de Farmacologia, Facultad de Medicina, Universitat de València, Spain.
Eur J Pharmacol. 1994 Apr 1;255(1-3):157-65. doi: 10.1016/0014-2999(94)90094-9.
The effects of Ca2+ channel antagonists and benzodiazepine receptor ligands against concentration-dependent contractions of rat urinary bladder induced by CaCl2 (0.1-50 mM, in K(+)-depolarized tissues), KCl (1-100 mM) and acetylcholine (0.1 microM to 1 mM) were studied. Nifedipine (0.001-0.1 microM), verapamil (0.01-1 microM), diltiazem (0.01-1 microM), cinnarizine (1-100 microM), and trifluoperazine (1-100 microM) 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 bladder, was nifedipine (0.01 microM) > diltiazem (0.36 microM) approximately verapamil (0.41 microM) > or = cinnarizine (2.57 microM) > trifluoperazine (17.4 microM). These antagonists depressed KCl-induced contractions with an effectiveness and potency similar to that displayed against CaCl2-induced contractions. Nifedipine, verapamil, and diltiazem but not cinnarizine and trifluoperazine had a preferential inhibitory effect on the contractions elicited by KCl when compared to those elicited by acetylcholine. Ro 5-4864, diazepam, midazolam and the non-benzodiazepine PK 11195, each at 1-100 microM, depressed CaCl2- and KCl-induced contractions (IC50 values in the micromolar range). Benzodiazepines and PK 11195, all at 100 microM, markedly depressed acetylcholine-induced contractions. Flumazenil was scarcely effective. Cinnarizine (100 microM) and trifluoperazine (100 microM), but not the other Ca2+ channel antagonists and benzodiazepine receptor ligands tested, depressed Ca2+ (20 microM)-evoked contractions of skinned bladder. It is concluded that the action of nifedipine, verapamil, and diltiazem is restricted to the plasmalemma whereas cinnarizine and trifluoperazine also act on the intracellular contractile apparatus.(ABSTRACT TRUNCATED AT 250 WORDS)
研究了钙离子通道拮抗剂和苯二氮䓬受体配体对氯化钙（0.1 - 50 mM，在钾离子去极化组织中）、氯化钾（1 - 100 mM）和乙酰胆碱（0.1 μM至1 mM）诱导的大鼠膀胱浓度依赖性收缩的影响。硝苯地平（0.001 - 0.1 μM）、维拉帕米（0.01 - 1 μM）、地尔硫䓬（0.01 - 1 μM）、桂利嗪（1 - 100 μM）和三氟拉嗪（1 - 100 μM）均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，以针对钙离子（25 mM）诱导的去极化膀胱收缩的IC50衡量，为硝苯地平（0.01 μM）>地尔硫䓬（0.36 μM）≈维拉帕米（0.41 μM）≥桂利嗪（2.57 μM）>三氟拉嗪（17.4 μM）。这些拮抗剂抑制氯化钾诱导的收缩的有效性和效价与对氯化钙诱导的收缩相似。与乙酰胆碱诱导的收缩相比，硝苯地平、维拉帕米和地尔硫䓬对氯化钾诱导的收缩有优先抑制作用，而桂利嗪和三氟拉嗪则没有。Ro 5 - 4864、地西泮、咪达唑仑和非苯二氮䓬类药物PK 11195，均在1 - 100 μM时，抑制氯化钙和氯化钾诱导的收缩（IC50值在微摩尔范围内）。苯二氮䓬类药物和PK 11195，均在100 μM时，显著抑制乙酰胆碱诱导的收缩。氟马西尼几乎无效。桂利嗪（100 μM）和三氟拉嗪（100 μM），但不是其他测试的钙离子通道拮抗剂和苯二氮䓬受体配体，抑制钙离子（20 μM）诱发的脱细胞膀胱收缩。得出结论，硝苯地平、维拉帕米和地尔硫䓬的作用局限于质膜，而桂利嗪和三氟拉嗪也作用于细胞内收缩装置。（摘要截短至250字）
