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苯妥英对药物及钙诱导的大鼠离体子宫收缩的影响:与硝苯地平的比较研究

Effect of diphenylhydantoin on drug and calcium induced contractions of isolated rat uterus: a comparative study with nifedipine.

作者信息

Calixto J B

出版信息

Gen Pharmacol. 1987;18(3):237-43. doi: 10.1016/0306-3623(87)90005-x.

DOI:10.1016/0306-3623(87)90005-x
PMID:2436973
Abstract

The sustained contractions induced by K+, acetylcholine (ACh) and oxytocin (Ot) were inhibited in a concentration-dependent fashion by diphenylhydantoin (DPH) and nifedipine (NIF) in the following order of sensitivity: K+ greater than ACh greater than Ot. Previous incubation of DPH and NIF produced a non-competitive antagonism towards ACh and Ot-induced contractions. Increasing of calcium (Ca2+) concentration (0.2-1.5 mM) completely reverse the inhibitory effect of DPH and NIF, suggesting a competitive type of antagonism, between Ca2+ and DPH. A clear difference between DPH and NIF actions was observed when the K+-depolarizing solution was used. In this condition, DPH caused a parallel and concentration-related rightward displacement of the dose-response curves of Ca2+ (pA2 = 4.91 +/- 0.1), while NIF produced a rightward displacement allied to a significant reduction of the Ca2+ maximal response. DPH, but not NIF, produced a concentration-dependent relaxation in sustained contraction induced by Ca2+ (1 mM) in depolarized tissue.

摘要

苯妥英(DPH)和硝苯地平(NIF)以浓度依赖的方式抑制由钾离子(K⁺)、乙酰胆碱(ACh)和催产素(Ot)诱导的持续收缩,其敏感性顺序如下:K⁺>ACh>Ot。预先孵育DPH和NIF会对ACh和Ot诱导的收缩产生非竞争性拮抗作用。增加钙(Ca²⁺)浓度(0.2 - 1.5 mM)可完全逆转DPH和NIF的抑制作用,表明Ca²⁺与DPH之间存在竞争性拮抗作用。当使用K⁺去极化溶液时,观察到DPH和NIF作用之间存在明显差异。在这种情况下,DPH导致Ca²⁺剂量 - 反应曲线平行且与浓度相关的右移(pA2 = 4.91 ± 0.1),而NIF产生右移并伴有Ca²⁺最大反应的显著降低。在去极化组织中,DPH而非NIF在由Ca²⁺(1 mM)诱导的持续收缩中产生浓度依赖性舒张。

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