Central nervous stimuli increase duodenal bicarbonate secretion by release of mucosal melatonin.
A number of common diseases in humans, including gastroduodenal ulcer and irritable bowel syndrome, show circadian rhythms in pain and discomfort. The neurohormone melatonin is released from enterochromaffin cells in the intestinal mucosa and from the pineal gland but its role in gastrointestinal function is largely unknown. We have studied the involvement of melatonin in stimulation of the mucosa-protective alkaline secretion by the duodenal mucosa. A 12-mm segment of proximal duodenum with an intact blood supply was cannulated in situ in anesthetized rats and duodenal HCO3- secretion titrated by pH-stat. Duodenal close intra-arterial infusion of melatonin or the full agonist 2-iodo-N-butanoyl- 5-methoxytryptamine significantly increased the secretion and pretreatment with the melatonin (predominantly MT2-receptor specific) antagonist luzindole almost abolished the response. Intracerebroventricular (i.c.v.) infusion of the alpha1-adrenoceptor agonist phenylephrine (12.2 micromol kg(-1) x h(-1)) caused an up to fivefold increased in the alkaline secretion and the melatonin antagonist luzindole or cutting all peri-carotid nerves abolished the duodenal secretory response to i.c.v. phenylephrine. Peripheral melatonin thus stimulates duodenal mucosal HCO3- secretion and endogenous melatonin, very likely released from mucosal enterochromaffin cells, is involved in mediating neural stimulation of the secretion.
Sjöblom
M
M
Department of Physiology, Uppsala University, Sweden.
Flemström
G
G
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D044094:Receptors, Melatonin
D001639:Bicarbonates; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; D008550:Melatonin