Central nervous α1-adrenoceptor stimulation induces duodenal luminal release of melatonin

Intracerebroventricular (i.c.v.) infusion of the alpha(1)-adrenoceptor agonist phenylephrine elicits vagal and sympathetic neural stimulation of the bicarbonate secretion by the duodenal mucosa. Melatonin originating from mucosal enterochromaffin cells (EC cells) has been proposed to mediate this centrally elicited stimulation. However, the release of intestinal melatonin has not been studied. Rats were anesthetized with thiobarbiturate, a 12-mm segment of duodenum with intact blood supply was cannulated in situ and bicarbonate secretion titrated by pH-stat. The mean arterial blood pressure was continuously recorded. Melatonin in the duodenal luminal perfusate was determined by high-performance liquid chromatography with electrochemical detection. Intracerebroventricular infusion of phenylephrine (12.2 mumol/kg/hr) induced more than 10-fold increase in release of melatonin into the duodenal lumen and an increase in HCO3- secretion from 7.6 +/- 0.5 to 18.6 +/- 2.1 muEq/cm/hr. The melatonin receptor (MT2 > MT1) antagonist luzindole (600 nmol/kg, i.v.) almost abolished the marked rise in bicarbonate secretion induced by i.c.v. phenylephrine but, in contrast, did not affect the release of melatonin. These results strongly suggest that release of melatonin from the mucosa mediates the duodenal secretory response to centrally elicited neural stimulation.