Functional characterization of serotonin receptor subtypes in human duodenal secretion.
Serotonin (5-HT) stimulates ion secretion in the gastrointestinal tract and the sensitivity for 5-HT might be altered in dyspeptic patients infected with Helicobacter pylori. The purpose of the present study was to characterize the 5-HT-induced electrogenic ion transport in the duodenum of dyspeptic patients with or without Helicobacter pylori infection, and to determine the 5-HT receptor subtypes functionally involved. Biopsies from the second part of duodenum were obtained from 43 dyspeptic patients during routine endoscopy. Biopsies were mounted in modified Ussing chambers with air suction for measurements of short-circuit current by a previously validated technique. Short-circuit current was measured before and after application of graded cumulative doses of 5-HT and a single dose of bumetanide (an inhibitor of chloride/bicarbonate transport), or one of the selective 5-HT receptor antagonists: ketanserin, ondansetron, or SB-204070 (1-butyl-4 piperidinmethyl-8-amino-7-chloro-2,3-dihydro-1,4-benzodioxin-5-carboxylate HCl). Histological examination was performed on duodenal biopsies. Helicobacter urease testing and histological examination determined Helicobacter pylori infection. 5-HT induced a dose-dependent and bumetanide-sensitive short-circuit current, which was independent of the presence of Helicobacter pylori infection. All the three 5-HT receptor antagonists failed to significantly effect basal and 5-HT-induced short-circuit current. Our results indicate that in human duodenum 1) 5-HT is a potent stimulator of bumetanide-sensitive secretion, 2) the serotonergic receptor subtype, which acts as the main mediator of 5-HT-induced secretion is different from the 5-HT(2), 5-HT(3), and the 5-HT(4) subtype and, 3) the sensitivity to 5-HT is not altered by Helicobacter pylori infection.
Engelmann
Bodil Elisabeth
BE
Department of Gastrointestinal Surgery D, University Hospital of Glostrup, Copenhagen, Denmark.
Bindslev
Niels
N
Poulsen
Steen Seier
SS
Larsen
Rune
R
Hansen
Mark Berner
MB
D000328:Adult; D000368:Aged; D002034:Bumetanide / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D005260:Female; D016481:Helicobacter Infections / Q000378:metabolism; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D066298:In Vitro Techniques; D007419:Intestinal Secretions; D017136:Ion Transport / Q000187:drug effects; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D017294:Ondansetron / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology
D004146:Dioxanes; D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D049994:Sodium Potassium Chloride Symporter Inhibitors; D002034:Bumetanide; C084858:SB 204070A; D012701:Serotonin; D017294:Ondansetron; D007650:Ketanserin