Melatonin in the duodenal lumen is a potent stimulant of mucosal bicarbonate secretion

Abstract

Melatonin, originating from intestinal enterochromaffin cells, mediates vagal and sympathetic neural stimulation of the HCO3- secretion by the duodenal mucosa. This alkaline secretion is considered the first line of mucosal defense against hydrochloric acid discharged from the stomach. We have studied whether luminally applied melatonin stimulates the protective secretion and whether a melatonin pathway is involved in acid-induced stimulation of the secretion. Rats were anaesthetized (Inactin®) and a 12-mm segment of proximal duodenum with an intact blood supply was cannulated in situ. Mucosal HCO3- secretion (pH-stat) and the mean arterial blood pressure were continuously recorded. Luminal melatonin at a concentration of 1.0 μM increased (P < 0.05) the secretion from 7.20 ± 1.35 to 13.20 ± 1.51 μEq/cm/hr. The MT2 selective antagonist luzindole (600 nmol/kg, i.v.) had no effect on basal HCO3- secretion, but inhibited (P < 0.05) secretion stimulated by luminal melatonin. Hexamethonium (10 mg/kg i.v. followed by continuous i.v. infusion at a rate of 10 mg/kg/hr), abolishes neurally mediated rises in secretion and also inhibited (P < 0.05) the stimulation by luminal melatonin. Exposure of the lumen to acid containing perfusate (pH 2.0) for 5 rain increased (P < 0.05) the HCO3- secretion from 5.85 ± 0.82 to 12.35 ± 1.51 μEq/cm/hr, and luzindole significantly inhibited (P < 0.05) this rise in secretion. The study thus demonstrates that luminal melatonin is a potent stimulant of duodenal HCO3- secretion and, furthermore, strongly suggests melatonin as an important mediator of acid-induced secretion.