Kim C H, Zinsmeister A R, Malagelada J R
Gastroenterology. 1987 Apr;92(4):993-9. doi: 10.1016/0016-5085(87)90975-9.
We postulated that local synthesis and release of prostaglandins might be the paracrine pathway that triggers gastric dysrhythmia when exogenously activated. The study was divided into three parts. In part 1, a dose-response study was performed in 7 dogs to estimate the 95% effective dose for four pharmacologic agents known to cause gastric dysrhythmia. In part 2, we determined the relative efficacy of three putative blockers in preventing pharmacologic induction of gastric dysrhythmia. In part 3, several ancillary experiments were performed. The results show that an intraarterial bolus of epinephrine, met-enkephalin, prostaglandin E2, and glucagon each induced episodes of gastric dysrhythmia, whereas saline injections did not. The 95% effective dose of these dysrhythmic drugs were 10.5, 77.0, 35.0, and 407.0 micrograms/kg, respectively. The dysrhythmic action of epinephrine was blocked by phentolamine and indomethacin but not by naloxone. The dysrhythmic action of met-enkephalin was blocked by naloxone and indomethacin but not by phentolamine. The dysrhythmic action of glucagon was not blocked by phentolamine, naloxone, or indomethacin. The inhibitory effect of indomethacin on epinephrine-induced gastric dysrhythmia was shared by meclofenamate. Thus, we conclude that local prostaglandins mediate the production of gastric dysrhythmias by epinephrine and met-enkephalin; however, glucagon causes gastric dysrhythmias by a non-prostaglandin-mediated mechanism.
我们推测，前列腺素的局部合成与释放可能是在外源性激活时引发胃节律紊乱的旁分泌途径。本研究分为三个部分。在第一部分中，对7只犬进行了剂量反应研究，以估算已知可引起胃节律紊乱的四种药物的95%有效剂量。在第二部分中，我们确定了三种假定阻滞剂在预防药物诱导的胃节律紊乱方面的相对疗效。在第三部分中，进行了几项辅助实验。结果表明，动脉内推注肾上腺素、甲硫氨酸脑啡肽、前列腺素E2和胰高血糖素均可诱发胃节律紊乱发作，而注射生理盐水则不会。这些致心律失常药物的95%有效剂量分别为10.5、77.0、35.0和407.0微克/千克。肾上腺素的致心律失常作用可被酚妥拉明和吲哚美辛阻断，但不能被纳洛酮阻断。甲硫氨酸脑啡肽的致心律失常作用可被纳洛酮和吲哚美辛阻断，但不能被酚妥拉明阻断。胰高血糖素的致心律失常作用不能被酚妥拉明、纳洛酮或吲哚美辛阻断。甲氯芬那酸也具有吲哚美辛对肾上腺素诱导的胃节律紊乱的抑制作用。因此，我们得出结论，局部前列腺素介导肾上腺素和甲硫氨酸脑啡肽引起的胃节律紊乱；然而，胰高血糖素通过非前列腺素介导的机制引起胃节律紊乱。
