Adrenomedullin inhibits gastric acid secretion and motility in rat

Abstract

Aim of the study; Adrenomedullin(AM) is a novel hypotensive peptide discovered by Kitamura et al in 1993. It was reported that AM exists in the digestive tract, but nothing is known about the physiological effects of AM in the stomach. We evaluate the effect of intravenous injection of AM on the gastric acid secretion and motility in rat. Methods; Male Wistar rats weighing 200 to 250 g were fastened for 24 h but allowed free access to water up to the beginning of the experiment. 1) Gastric acid secretion: Under urethane anesthesia (1.7g/kg;IP), the physiological saline (pH 7.0 -+ 0.14) was infused through the polyethylene catheter via oral, the gastric secretion was collected continuously through the gastric eannula implanted in the pylorus (lml/min), the gastric acid output and the pepsin activity were measured for every 5min. The gastric acid secretion was stimulated by the infusion of pentagastrin (PG:16~tg/kg/h) for the duration of the experiment and rat-AM was injected through the femoral vein after the stable value of the gastric acid output. 2) Gastric motility: Under urethane anesthesia, the intra-gastric pressure (IGP) and motility were measured by the rubber balloon implanted through an incision in the forestomach and rat-AM was injected through the femoral vein after the stable value of the IGP. CGRP(8-37) was preadministrated, vagotomy and adrenectomy were performed to evaluate the mechanism of this action in the stomach, respectively. Result ; 1) AM did not effect basal gastric secretion (0.9 + 0.04laM/5min). AM inhibited the pentagasrin-stimulated gastric acid secretion significantly, but pepsin activity was not changed. These effects were dose-dependent and not prevented by CGRP(8-37), vagotomy and adrenectomy. 2)AM decreased the basal IGP and gastric motility, significantly. These effects were dose-dependent but not suppressed by CGRP(8-37), vagotomy, adrenectomy.