Agmatine, an endogenous imidazoline receptor agonist, increases gastric secretion and worsens experimental gastric mucosal injury in rats.

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.