二氢吡啶类钙拮抗剂Mn9202对5-HT收缩胃底平滑肌的影响

Inhibitory effect of Mn9202 on 5-HT induced contraction of rat stomach fundus

目的 研究新的二氢吡啶类钙拮抗剂 Mn92 0 2对 5 -HT引起胃底平滑肌收缩的影响 .方法 通过离体实验 ,观察不同浓度的 Mn92 0 2 (1,10μmol· L- 1 )孵育时 5 - HT的量效曲线 ,以及 Ca2 + 的影响 ,同时与胃底平滑肌 5 - HT竞争性拮抗剂米安舍林 (m ianserin) [1 ]对比 .结果 细胞外钙减少 ,5 - HT收缩胃底平滑肌的量效曲线的最大效应降低 ,但 5 - HT的浓度范围不变 ;Mn92 0 2呈剂量依赖性地使 5 - HT的最大反应降低 ,并使曲线右移 ,分别使最大反应降低至 (75± 1.8) %和(5 5± 3.2 ) % ,除去细胞外钙时 ,Mn92 0 2 1μm ol·L- 1使 5 - HT的量效曲线右移至 3× 10 - 3 ,最大反应降低至原来的 18% ,此时在灌流液中加入 2 .5 mol· L- 1 Ca Cl2 ,最大反应上升为原来的 60 % .mianserin使 5 - HT的量效曲线平行右移 ,最大反应不变 .Mn92 0 2能够取消 mianserin对 5 - HT的拮抗作用 .结论 在大鼠的胃底平滑肌 ,Mn92 0 2能够非特异性地拮抗5 - HT的作用 ,这种作用与细胞外钙有关 ,同时也与非竞争性地拮抗 5 - HT2

AIM To study the antagonistic effects of Mn9202 on the contraction of rat stomach fundus caused by 5 HT. METHODS Effect of Mn9202 on cumulative concentration effect curves elicited by 5 HT, and the influence of Ca 2+ were observed, and then compared with mianserin which is the competitive antagonist of 5 HT. RESULTS Decreasing [Ca 2+ ] from a control value of 5 mmol·L -1 to 1 mmol·L -1 , the upper end of the dose response curve of 5 HT was lowered without affecting threshold 5 HT doses. In a concentration dependent manner, Mn9202 shifted the cumulative dose response curves of 5 HT to right and reduced the efficacy of 5 HT to (75±1.8)% and (55±3.2)% respectively. Removing the extrocellular, Mn9202 (1 μmol·L -1 ) shifted the curve to right and reduced the efficacy to 18%. Mianserin shifted the curve to right at the same level. And Mn9202 blocked the 5 HT 2 receptor antagonist action of mianserin. CONCLUSION In the rat stomach fundus, Mn9202 can antagonize 5 HT nonspecificly and this effect is related to the blockade of extrocellular Ca 2+ and the nonsurmountable antagonist effect of 5 HT 2.