Influence of ondansetron on gastric sensorimotor responses to short duodenal acid infusion in healthy volunteers.
BACKGROUND
Duodenal acid infusion induces gastric relaxation and sensitization to distension in healthy volunteers. The acid-sensitive mechanism is still unknown. We hypothesized that 5HT(3)-blockade can inhibit the acid-induced duodenogastric sensorimotor reflex in healthy volunteers.


METHODS
Fourteen healthy volunteers were included in a randomized, double-blind placebo-controlled cross-over trial. An infusion tube with attached pH-electrode was positioned in the duodenum and a barostat balloon was located in the gastric fundus. Proximal gastric volume and sensitivity to distension were assessed before and during duodenal acid infusion and after pretreatment with intravenous (i.v.) ondansetron (a 5HT(3)-receptor antagonist, 8 mg) or saline. An overall perception score (0-6) and an assessment of nine dyspeptic symptoms by visual analogue scales (VAS) were obtained. Results are given as mean ± SEM.


RESULTS
Ondansetron had no effect on duodenal pH and on the acid-induced increase of proximal gastric volume (increase of 80 ± 20 vs 83 ± 15 mL after ondansetron and placebo; effect of acid <0.001, between treatments ns). After ondansetron, the overall perception score during duodenal acidification and gastric distension was significantly decreased compared with placebo (P=0.01). There was no effect of ondansetron on the individual dyspeptic symptoms.


CONCLUSIONS
Ondansetron decreased gastric sensitivity during duodenal acid infusion and gastric distension. 5HT(3)-receptors are involved in acid-induced duodenogastric sensitization, but not in the duodenogastric inhibitory motor reflex.
Center for Gastroenterological Research, University Hospital Gasthuisberg, University of Leuven, Leuven, Belgium.
T
T
Vanuytsel
G
G
Karamanolis
L
L
Van Oudenhove
L V
LV
Oudenhove
R
R
Vos
J
J
Tack
D000143:Acids / Q000494:pharmacology*; D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004386:Duodenum / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008365:Manometry / Q000295:instrumentation / Q000379:methods; D009129:Muscle Tonus / Q000187:drug effects; D017294:Ondansetron / Q000494:pharmacology*; D010919:Placebos; D011312:Pressure; D012018:Reflex; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects* / Q000502:physiology*; D055815:Young Adult
D000143:Acids; D010919:Placebos; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists; D017294:Ondansetron