Peripheral melatonin mediates neural stimulation of duodenal mucosal bicarbonate secretion

Abstract

Melatonin is released from intestinal enterochromaffin cells and from the pineal gland, but its role in gastrointestinal function is largely unknown. Our aim was to study the involvement of intestinal and central nervous melatonin in the neurohumoral control of the duodenal mucosa-protective bicarbonate secretion. Working in anesthetized rats, we cannulated a 12-mm segment of duodenum with an intact blood supply and titrated the local bicarbonate secretion with pH-stat. Melatonin and receptor ligands were supplied to the duodenum by close intra-arterial infusion. Even at low doses, melatonin and the full agonist 2-iodo-N-butanoyl-5-methoxytryptamine increased duodenal bicarbonate secretion. Responses were inhibited by the predominantly MT 2 -selective antagonist luzindole but not by prazosin, acting at MT 3 receptors. Also, luzindole almost abolished the marked rise in secretion induced by intracerebroventricular infusion of the adrenoceptor agonist phenylephrine. This response was also abolished by sublaryngeal ligation of all nerves around the carotid arteries. However, it was insensitive to truncal vagotomy alone or sympathectomy alone and was unaffected by removal of either the pineal gland or pituitary gland. Thus, melatonin stimulates duodenal bicarbonate secretion via action at enterocyte MT 2 -receptors and mediates neural stimulation of the secretion.

Melatonin inhibits alcohol-induced increases in duodenal mucosal permeability in rats in vivo

“…To assess whether endogenous melatonin take part in the mediation of the ethanol-induced increase in duodenal epithelial permeability and motility, the melatonin MT 1 /MT 2 receptor antagonist luzindole was used. It has previously been shown that a single iv bolus dose of 0.17 mg/kg luzindole abolish melatonin-induced stimulation of duodenal mucosal bicarbonate secretion (45,46). In addition, we have also shown that luzindole (0.17 mg/kg) does not affect basal duodenal paracellular permeability or duodenal motility (48).…”

Short fasting dramatically decreases rat duodenal secretory responsiveness to orexin A but not to VIP or melatonin

“…The HCO 3 Ϫ secretion is under central as well as peripheral neurohumoral influence, and intracerebroventricular administration of some neuropeptides and the ␣ 1 -selective adrenoceptor agonist phenylephrine stimulates the duodenal secretion in the rat (10,12,25,42). The centrally elicited secretory responses are mediated by vagal and sympathetic neural pathways and by release of ␤-endorphin from the pituitary gland.…”

“…Subsequently, the rats were tracheotomized with a tracheal tube to facilitate respiration, and body temperature was maintained at 37-38°C throughout experiments by a heating pad controlled by a rectal thermistor probe. The surgical and experimental procedures have been described previously (12,42). A brief summary is given, and some modifications are described here.…”

“…All secretagogues were administered to the duodenum by close intra-arterial infusion, described previously by Sjöblom et al (42). Only small amounts of the compounds were thus required, minimizing any central nervous action.…”

“…The total amount of melatonin present in the intestine is thus ϳ400ϫ larger than in the central nervous system (5,17,34). Recent studies from our group have shown that melatonin, acting at MT 2 receptors, stimulates mucosal HCO 3 Ϫ secretion in rat duodenum in vivo (41,42) and, in addition, mediates centrally elicited neural stimulation of the alkaline secretion (42). Melatonin also induces intracellular calcium ([Ca 2ϩ ] i ) signaling in isolated human and rat duodenal enterocytes, strongly suggesting an action at enterocyte membrane receptors (43).…”