Peripheral melatonin mediates neural stimulation of duodenal mucosal bicarbonate 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 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.
Sjöblom
M
M
Department of Physiology, Uppsala University, Uppsala, Sweden.
Jedstedt
G
G
Flemström
G
G
D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D002940:Circadian Rhythm; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism*; D004759:Enterochromaffin Cells / Q000378:metabolism*; D007016:Hypophysectomy; D007269:Injections, Intra-Arterial; D007276:Injections, Intraventricular; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D008550:Melatonin / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D009489:Neurosecretion / Q000187:drug effects / Q000502:physiology*; D010656:Phenylephrine / Q000008:administration & dosage / Q000494:pharmacology; D010870:Pineal Gland / Q000601:surgery; D011224:Prazosin / Q000008:administration & dosage / Q000494:pharmacology; D020033:Protein Isoforms / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000502:physiology; D044094:Receptors, Melatonin; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000494:pharmacology; D013874:Thiopental / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D014363:Tryptamines / Q000008:administration & dosage / Q000494:pharmacology; D014628:Vagotomy; D019825:gamma-MSH / Q000008:administration & dosage / Q000494:pharmacology
C114459:4-phenyl-2-propionamidotetraline; D001639:Bicarbonates; D020033:Protein Isoforms; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; D013764:Tetrahydronaphthalenes; D014363:Tryptamines; D019825:gamma-MSH; C057154:luzindole; D010656:Phenylephrine; C004316:thiobutabarbital; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D013874:Thiopental; D008550:Melatonin; D011224:Prazosin