Introduction
Bicarbonate secretion by the duodenal mucosa is considered the primary mechanism in duodenal protection against acid discharged from the stomach. We have recently shown that intracerebroventricular infusion of the alpha-1 adrenoceptor agonist phenylephrine is a potent stimulant of duodenal mucosal bicarbonate secretion. Intravenous administration of the compound, in contrast, increases blood pressure but is without effect on duodenal secretion. The purpose of this study was to examine the effects of melatonin and some melatonin receptor ligands on duodenal bicarbonate secretion.
Methods
Rats were anaesthetised with thiobarbiturate and a 12 mm segment of proximal duodenum with an intact blood supply was cannulated in situ. Duodenal mucosal bicarbonate secretion (pH stat) and the mean arterial blood pressure were recorded continuously. Agents were administered; 1) close intra-arterially; 2) into the lateral ventricle in the central nervous system; or 3) intravenously. For close intra-arterial infusion to the duodenum, the hepatic artery was cannulated, tied before its entrance into the liver and perfused in retrograde direction.
Results
Close intra-arterial infusion of melatonin to the duodenum (20-200 nmol/kg,h) caused a dose-dependent (up to three-fold) increase in mucosal bicarbonate secretion. Intracerebroventricular melatonin (4 nmol/h), in contrast, did not affect the secretion. Intracerebroventricular phenylephrine (2,500 µg/kg,h) caused a three-fold increase in the alkaline secretion in normal rats and a somewhat smaller increase (two-fold) in hypophysectomised rats. The melatonin receptor antagonist Luzindole (600 nmol/kg, intravenously) had no effect on basal bicarbonate secretion, but significantly inhibited secretion stimulated by local (intra-arterial) melatonin, in addition Luzindole abolished the response to intracerebroventricular phenylephrine. Hypophysectomy had no or little effect on basal duodenal secretion or the secretory response to central phenylephrine.
Conclusions
Melatonin stimulates duodenal mucosal bicarbonate secretion and is likely one of the mediators of the central nervous influence on duodenal protection. This may, in theory, contribute to circadian rhythmicities in mucosal vulnerability to acid injury.
References