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 MT2-selective antagonist luzindole but not by prazosin, acting at MT3 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 MT2-receptors and mediates neural stimulation of the secretion.

Food-induced expression of orexin receptors in rat duodenal mucosa regulates the bicarbonate secretory response to orexin-A

“…It should also be noted that the hepatic branch that enters the duodenum via the perivascular plexuses of the hepatic, gastroduodenal, and superior pancreaticoduodenal arteries innervates primarily the duodenum. Previous studies with the present type of in situ chamber preparation have shown that intracerebroventricular administration of the peptide hormone TRH (16,30) or the catecholamine phenylephrine (28,44) induces vagally mediated stimulation of duodenal alkaline secretion. Furthermore, it has been shown that electrical stimulation of the cut cervical vagal nerves in the distal direction does stimulate the secretion in rat and also cat duodenum in situ (22,36).…”

“…Animals were tracheotomized, and body temperature was maintained at 37-38°C throughout the experiments by a heating pad controlled by a rectal thermistor probe. The surgical and experimental protocols have been described fully previously (13,16,44). A brief summary and some modifications are described here.…”

“…Orexin-A was administered to the duodenum by close intra-arterial infusion, described previously (44). Only small amounts of the compound were thus required, minimizing any central nervous actions.…”

Epithelial Cells and Their Neighbors. II. New perspectives on efferent signaling between brain, neuroendocrine cells, and gut epithelial cells

“…Intracerebroventricular administration of the adrenoceptor agonist phenylephrine acting at ␣ 1 -adrenoreceptors causes a marked, up to fivefold, increase in duodenal mucosal HCO 3 Ϫ secretion (12,25,26). Pretreatment with prazosin, an ␣ 1 -antagonist, inhibited this rise in secretion when infused into the lateral brain ventricle but not when administered intravenously, confirming that the stimulatory action of phenylephrine is centrally elicited (12).…”

“…It has thus been the subject of several studies (2). It is now clear that centrally elicited stimulation of the HCO 3 Ϫ secretion occurs on intracerebroventricular infusion of some neuropeptides and catecholamines, including thyrotropin-releasing hormone (TRH), corticotropin-releasing hormone, and phenylephrine (6,(12)(13)(14)26). In contrast, intracerebroventricular infusion of calcitonin gene-related peptide (13) or the adrenoceptor agonist clonidine (12) inhibits the mucosal HCO 3 Ϫ secretion.…”