Effect of selective 5HT3 antagonist (GR 38032F) on small intestinal transit and release of gastrointestinal peptides

N. J. Talley, S. F. Phillips, A. Haddad, L. J. Miller, C. Twomey, A. R. Zinsmeister, A. Ciociola

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Antagonists of 5-hydroxytryptamine type 3 (5HT3) receptors reduce the nausea induced by cisplatinum, but the effects of these agents on 5HT3 receptors in the human gut remain to be defined. We examined the actions of one of these drugs (Glaxo GR 38032F) on small intestinal transit and mouth-to-cecum transit times in healthy man. We also quantified its effects on the release of peptide YY (PYY), neurotensin, human pancreatic polypeptide, gastrin-cholecystokinin, and motilin. Ten healthy volunteers were enrolled in a randomized, double-blind, placebo-controlled crossover study. Following a single intravenous dose of GR 38032F (0.15 mg/kg), we measured the time to appearance in plasma of sulfapyridine after injection of salicylazosulfapyridine into the duodenum. This was used as a measure of duodenocecal transit. The appearance of hydrogen in breath after ingestion of a meal containing lactulose was also correspondingly used to quantify the mouth-to-cecum transit of the "head" of the meal. Gastrointestinal hormones were assayed in plasma by specific RIAs; samples were drawn fasting (10 min after injection) and after breakfast (358 calories: 15.7 g protein, 55.4 g carbohydrate, 8.1 g fat). The postprandial integrated response and peak release of PYY was decreased by GR 38032F. There was also a trend for the peak release of neurotensin to be reduced. GR 38032F did not significantly alter small intestinal transit times or mouth-to-cecum transit times. We conclude that GR 38032F does not have a major effect on small intestinal transit in health.

Original languageEnglish (US)
Pages (from-to)1511-1515
Number of pages5
JournalDigestive Diseases and Sciences
Volume34
Issue number10
DOIs
StatePublished - Oct 1 1989

Keywords

  • 5-hydroxytryptamine
  • intestinal peptides
  • motility
  • small bowel transit

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

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