Influence of ghrelin on interdigestive gastrointestinal motility in man

Jan Tack ^1*, Inge Depoortere ², Raf Bisschops ³, C Delporte ⁴, Bernard Coulie ⁵, Ann Meulemans ⁵, Jozef Janssens ² and Theo Peeters ²

¹ University Hospital Gasthuisberg, Belgium
² University of Leuven, Belgium
³ University Hospitals Leuven, Belgium
⁴ Universite Libre de Bruxelles, Belgium
⁵ Janssen Research Foundation, Belgium

^* To whom correspondence should be addressed. E-mail: jan.tack{at}med.kuleuven.ac.be.

Accepted 28 August 2005

Abstract

Background: Recent studies in animals have shown that ghrelin stimulates upper gastrointestinal motility through the vagus and through the enteric nervous system. The aim of the present study therefore was to simultaneously investigate the effect of administration of ghrelin on upper gastrointestinal motility and to elucidate its mode of action by measuring plasma levels of gastrointestinal hormones in man.

Materials and Methods: Nine healthy volunteers (4 m, age 22-35 yrs) underwent a combined antro-duodenal manometry and proximal stomach barostat study on 2 separate occasions, at least one week apart. Twenty minutes after the occurrence of phase III of the migrating motor complex (MMC), saline or ghrelin 40 mg were administered intravenously during 30 minutes in a double-blind randomized cross-over fashion. Ghrelin, motilin, pancreatic polypeptide, glucagon and somatostatin were measured by radioimmunoassay in blood samples drawn at 15-30 minute intervals. The influence of ghrelin or saline on MMC phases, hormone levels and intra- balloon volume was compared using paired t-test, ANOVA and Chi square testing.

Results: In all subjects, spontaneous phase III occurred, with a gastric origin in 4. Administration of ghrelin induced a premature phase III (12±3 min, p<0.001; gastric origin in 9, p<0.05), compared to saline (95±13 min, gastric origin in 2). Intra-balloon volumes before infusion were similar (135±13 vs. 119±13 ml, NS), but ghrelin induced a long-lasting decrease of intra-balloon volume (184±31 vs. 126±21 ml first 60 min, p<0.05). Administration of ghrelin increased plasma levels for pancreatic polypeptide and ghrelin, but motilin, somatostatin and glucagon levels were not altered.

Conclusions: In man, administration of ghrelin induces a premature gastric phase III of the MMC, which is not mediated through the release of motilin. This is accompanied by a prolonged increased tone of the proximal stomach.

Keywords: appetite control, gastric motility, gastrointestinal hormones, ghrelin, manometry

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