[Action of neurotensin on duodenal alkaline secretion in rats. Comparison with pancreatic and gastric secretion].
Neurotensin is released from endocrine N cells of the ileum after meals, and might take part in the regulation of bicarbonate secretion by the pancreas and duodenum. The aim of this study was to define the effect of neurotensin on duodenal bicarbonate secretion, in comparison with its effect on gastric and pancreatic secretions. Neurotensin produced a dose-related increase of duodenal bicarbonate secretion with an ED50 of 60 pmol/kg.h. The maximal effect (about 2 times the basal level) was observed with 600 pmol/kg.h. Equimolar doses (600 pmol/kg.h) of xenopsin, neuromedin N, neurotensin 8-13 produced the same effect as neurotensin 1-13. Neurotensin fragments 1-11 and 9-13 (600 pmol/kg.h) had no significant effect on duodenal bicarbonate secretion. Indomethacin, atropine, naloxone, or the CCK antagonist L364,718 had no effect on neurotensin-stimulated bicarbonate secretion. Hexamethonium and vagotomy reduced the neurotensin effect by about 50 percent (P less than 0.05). Neurotensin produced a dose-related increase of pancreatic bicarbonate secretion with an ED50 of 150 pmol/kg.h, a decrease of gastric acid secretion with an ED50 of 2,400 pmol/kg.h, and a decrease of gastric pepsin secretion with an ED50 of 2,760 pmol/kg.h. This study shows that neurotensin stimulates duodenal bicarbonate secretion in doses which may be physiological. This biological activity depends on the presence of the C-terminal 8-13 fragment. The mechanism is complex, and depends, for approximately half, on vagal fibers (sensitive or motor), nicotinic synapses, and a non cholinergic effector. The other half of the effect, still unexplained, could be a direct effect on mucosal cells. Pancreatic and duodenal bicarbonate secretions were more sensitive to neurotensin than gastric secretion (acid and pepsin).
Merlin
D
D
INSERM U239, Faculté de Médecine X.-Bichat, Paris.
Tazi-Saad
K
K
Nagain
C
C
Chariot
J
J
Rozé
C
C
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism; D005730:Ganglionic Blockers / Q000494:pharmacology; D005753:Gastric Mucosa / Q000378:metabolism*; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D008297:Male; D009496:Neurotensin / Q000031:analogs & derivatives / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical; D029867:Xenopus Proteins
D001639:Bicarbonates; D005730:Ganglionic Blockers; D006584:Hexamethonium Compounds; D009842:Oligopeptides; D010446:Peptide Fragments; D010455:Peptides; D029867:Xenopus Proteins; C042090:neuromedin N; D009496:Neurotensin; D018738:Hexamethonium; C016832:xenopsin
Action de la neurotensine sur la sécrétion bicarbonatée duodénale chez le rat. Comparaison avec les sécrétions pancréatique et gastrique.