Glavin G B, Carlisle M A, Smyth D D
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
J Pharmacol Exp Ther. 1995 Aug;274(2):741-4.
The present experiments tested the actions of a putative endogenous imidazoline receptor agonist, agmatine, on gastric secretion and on experimental gastric mucosal injury in rats. Agmatine, given i.p. (0.5-20.0 mg/kg) or i.c.v. (0.5-2.5 micrograms), augmented basal gastric acid secretion in conscious rats to a maximum of 40% when given i.p. and 44% when given i.c.v. Agmatine also potentiated total secretory volume as well as gastric acid and pepsin output in pylorus-ligated rats. When administered before exposure to stress, agmatine significantly decreased gastric glandular mucus levels and exacerbated stress-induced gastric mucosal injury. These results are in contrast to our data showing that an exogenous agonist of I1-imidazoline receptors, moxonidine, is a potent antisecretory and gastroprotective agent. A precise physiological role for agmatine in blood pressure regulation and in gastrointestinal function awaits clarification. However, it is possible that agmatine functions as an "inverse agonist" at central imidazoline receptors, resulting in hypertension, augmented gastric secretion and exacerbated gastric mucosal injury.
本实验检测了一种假定的内源性咪唑啉受体激动剂胍丁胺对大鼠胃液分泌及实验性胃黏膜损伤的作用。胍丁胺腹腔注射（0.5 - 20.0毫克/千克）或脑室内注射（0.5 - 2.5微克），可使清醒大鼠的基础胃酸分泌增加，腹腔注射时最高增加40%，脑室内注射时最高增加44%。胍丁胺还能增强幽门结扎大鼠的总分泌量以及胃酸和胃蛋白酶的分泌量。在暴露于应激之前给予胍丁胺，可显著降低胃腺黏液水平，并加重应激诱导的胃黏膜损伤。这些结果与我们的数据相反，我们的数据显示I1 - 咪唑啉受体的外源性激动剂莫索尼定是一种有效的抗分泌和胃保护剂。胍丁胺在血压调节和胃肠功能中的精确生理作用有待阐明。然而，胍丁胺有可能在中枢咪唑啉受体上作为“反向激动剂”发挥作用，导致高血压、胃酸分泌增加和胃黏膜损伤加重。
