Brage R, Cortijo J, Esplugues J, Esplugues J V, Martí-Bonmatí E, Rodriguez C
Br J Pharmacol. 1986 Dec;89(4):627-33. doi: 10.1111/j.1476-5381.1986.tb11166.x.
Experiments were designed to evaluate the effects of three calcium channel blockers (verapamil, diltiazem and cinnarizine) on gastric emptying and secretion in the rat. Pretreatment with the calcium blockers delayed gastric emptying of phenol red in a dose-dependent manner. Verapamil was the most effective of the agents tested. Verapamil and diltiazem inhibited gastric acid secretion in the pylorus-ligated rat without affecting pepsin output. Cinnarizine was ineffective in this model. When the perfused lumen of the anaesthetized rat was used, verapamil was found to inhibit responses to carbachol or histamine more than those to pentagastrin. Further, we found a greater sensitivity to verapamil for basal compared with vagal-stimulated (2-deoxy-D-glucose) acid secretion. Neither diltiazem nor cinnarizine modified gastric acid secretion in this experimental model. These findings are discussed in relation to the role of extracellular calcium in gastric motility and secretion, and the existence of a regional and functional selectivity for calcium blockers is proposed.
实验旨在评估三种钙通道阻滞剂(维拉帕米、地尔硫䓬和桂利嗪)对大鼠胃排空和分泌的影响。用钙阻滞剂预处理以剂量依赖性方式延迟了酚红的胃排空。维拉帕米是所测试药物中最有效的。维拉帕米和地尔硫䓬抑制幽门结扎大鼠的胃酸分泌,而不影响胃蛋白酶分泌量。桂利嗪在该模型中无效。当使用麻醉大鼠的灌注肠腔时,发现维拉帕米对卡巴胆碱或组胺反应的抑制作用比对五肽胃泌素反应的抑制作用更强。此外,我们发现与迷走神经刺激(2-脱氧-D-葡萄糖)引起的胃酸分泌相比,基础胃酸分泌对维拉帕米更敏感。在该实验模型中,地尔硫䓬和桂利嗪均未改变胃酸分泌。结合细胞外钙在胃运动和分泌中的作用对这些发现进行了讨论,并提出了钙阻滞剂存在区域和功能选择性的观点。