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 μg/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 meclof enamate. 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.
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