Escoubet B, Griffaton G, Samuel J L, Lechat P
Biochem Pharmacol. 1986 Dec 15;35(24):4401-7. doi: 10.1016/0006-2952(86)90755-0.
The effect of three calcium antagonists on the synthesis of prostacyclin (PGI2, assayed as 6-Keto-PGF1 alpha) and PGE2 by cultured rat cardiac myocytes and fibroblasts was investigated. In myocytes only, bepridil, diltiazem and verapamil (10(-9) to 10(-7) M) stimulated PGs synthesis by two- to three-fold, dose-dependently. At a concentration of 10(-6) or 10(-5) M the intensity of the stimulation of PGI2 and PGE2 decreased. Cobalt chloride (2 X 10(-3) M) did not change PGs synthesis (pg/mg of protein/30 min; means +/- SE, N = 10; PGE2: 365 +/- 59 and 463 +/- 89 treated vs controls; PGI2: 824 +/- 214 and 799 +/- 143 treated vs controls). After 30 min exposure of myocytes to hypoxic conditions (glucose-free medium and low PO2), the glycogen content was half that of the controls (P less than 0.001), ATP content did not change and PGI2 and PGE2 synthesis increased (X1.5, P less than 0.05). When applied to myocytes 30 min before inducing hypoxia, the three calcium antagonists stimulated PGs synthesis by three- to seven-fold at maximal effect, and bepridil (10(-8) M) or diltiazem (10(-7) M) prevented the hypoxia-induced decrease in glycogen content. With 10(-5) M drug concentration, the effect on PGs was not significant, except for the effect of bepridil on PGI2 (P less than 0.05). It is concluded that therapeutic concentrations of calcium antagonists simultaneously prevent the decrease in myocyte glycogen induced by hypoxia and stimulate PGs synthesis by myocytes.
研究了三种钙拮抗剂对培养的大鼠心肌细胞和成纤维细胞合成前列环素（PGI2，以6-酮-PGF1α测定）和PGE2的影响。仅在心肌细胞中，苄普地尔、地尔硫卓和维拉帕米（10^(-9)至10^(-7)M）以剂量依赖性方式刺激PGs合成增加2至3倍。在10^(-6)或10^(-5)M浓度下，PGI2和PGE2的刺激强度降低。氯化钴（2×10^(-3)M）未改变PGs合成（pg/毫克蛋白质/30分钟；均值±标准误，N = 10；PGE2：处理组与对照组分别为365±59和463±89；PGI2：处理组与对照组分别为824±214和799±143）。心肌细胞在缺氧条件（无糖培养基和低氧分压）下暴露30分钟后，糖原含量为对照组的一半（P＜0.001），ATP含量未改变，PGI2和PGE2合成增加（1.5倍，P＜0.05）。在诱导缺氧前30分钟应用于心肌细胞时，三种钙拮抗剂在最大效应时刺激PGs合成增加3至7倍，苄普地尔（10^(-8)M）或地尔硫卓（10^(-7)M）可防止缺氧诱导的糖原含量降低。在10^(-5)M药物浓度下，除苄普地尔对PGI2的作用外（P＜0.05），对PGs的影响不显著。结论是，治疗浓度的钙拮抗剂可同时防止缺氧诱导的心肌细胞糖原减少，并刺激心肌细胞合成PGs。
