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.

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.

. Short fasting dramatically decreases rat duodenal secretory responsiveness to orexin A but not to VIP or melatonin. Am J Physiol Gastrointest Liver Physiol 285: G1091-G1096, 2003. First published July 17, 2003 10.1152/ajpgi.00193.2003Orexins are involved in the central nervous control of appetite and behavior, and in addition, they are present in endocrine cells and/or neurons in the intestine. The role of these peptides in peripheral regulation of intestinal secretion has not been investigated. We thus compared the effects of orexin A and some established secretagogues on duodenal HCO 3 Ϫ secretion in fed rats with effects in rats exposed to short (overnight) food deprivation. Rats were anesthetized with thiobarbiturate, a 12-mm segment of proximal duodenum with intact blood supply was cannulated in situ, and the alkaline secretion was titrated by pH stat. Secretagogues were supplied specifically to the duodenum by close intra-arterial infusion. Orexin A (60-600 pmol ⅐ kg Ϫ1 ⅐ h Ϫ1 ) caused marked and dose-dependent stimulation of the duodenal secretion in fed animals but did not affect secretion in overnight food-deprived animals. Similarly, short fasting caused a 100-fold increase in the amount of the muscarinic agonist bethanechol (from 50 to 5,000 nmol ⅐ kg Ϫ1 ⅐ h Ϫ1 ) required for stimulation of the secretion. In contrast, the secretory responses to VIP (50-1,000 pmol ⅐ kg Ϫ1 ⅐ h Ϫ1 ) and melatonin (20-200 nmol ⅐ kg Ϫ1 ⅐ h Ϫ1 ) were not affected. The appetite-regulating peptide orexin A is thus a stimulant of intestinal secretion, but the response to this peptide as well as the muscarinic agonist bethanechol is markedly dependent on previous intake of food. Overnight fasting is a standard experimental procedure in studies of gastrointestinal function and pathophysiology in humans and animals. Studies made on neuroendocrine control of intestinal secretion may require reevaluation with respect to feeding status.bethanochol; bicarbonate secretion; duodenal mucosal protection; food deprivation; vasoactive intestinal polypeptide OREXINS WERE FIRST ISOLATED as hypothalamic appetiteincreasing peptides (9, 38) and appear to be involved in short-term regulation of feeding rather than long-term regulation of body weight (6, 46). Effects are mediated via two G protein-coupled receptors denoted OX 1 and OX 2 (21, 24). Orexins and receptors were also recently discovered in numerous endocrine (enterochromaffin) cells in the gastrointestinal tract and are present in the enteric nerves (21,24,27). The role of these compounds in peripheral regulation of intestinal function has, however, not been investigated in detail. Orexin cells in the hypothalamus are stimulated by fasting and inhibited by feeding (6). By tradition (32), experimental studies of gastrointestinal physiology and pathophysiology in humans and in intact animals have been conducted after overnight fast. Because the presence of food itself has a considerable effect of intestinal function (14), we have compared the actions of orexins and other intestinal se...

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We have studied the effects of intracerebral administration of selective alpha-adrenergic agonists on duodenal bicarbonate secretion. Duodenum free of Brunner's glands was cannulated in situ in anesthetized rats, and bicarbonate secretion into the luminal reperfusate was continuously titrated by pH stat. Infusion of the alpha 1-selective adrenoceptor agonist, phenylephrine (1,000-2,500 micrograms.kg-1.h-1), into a lateral brain ventricle increased (P < 0.01) duodenal bicarbonate secretion. Pretreatment with prazosin, an alpha 1-antagonist, significantly (P < 0.01) reduced the stimulatory effect when infused into the lateral ventricle (30 micrograms.kg-1.h-1), but not when administered intravenously (1,000 micrograms.kg-1.h-1). Hexamethonium (10 mg.kg-1.h-1 iv) abolished stimulation, whereas cervical vagotomy, epidural blockade, and naloxone were each without effect. Vasopressin, vasopressin antagonists, ts, and oxytocin did not affect basal secretion. Intracerebro-ventricular administration of the alpha 2-adrenoceptor agonist, clonidine (1,000 micrograms.kg-1.h-1), in contrast to alpha 1-receptor activation, decreased (P < 0.01) the secretion. Thus central nervous adrenoceptors influence duodenal mucosal bicarbonate te secretion, and alpha 1-adrenoceptor stimulation may provide protection against luminal acid. This potent stimulation was not mediated by the vagal nerves, spinal cord pathways, or the release of beta-endorphin but involves nicotinic, possibly enteric nervous transmission.