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Gastric motor effects of peptide and non-peptide ghrelin agonists in mice in vivo and in vitro
  1. T Kitazawa*,
  2. B De Smet,
  3. K Verbeke,
  4. I Depoortere,
  5. T L Peeters
  1. Centre for Gastroenterological Research, Catholic University of Leuven, Leuven, Belgium
  1. Correspondence to:
    Professor I Depoortere
    Centre for Gastroenterological Research, Gasthuisberg O&N, box 701, B-3000 Leuven, Belgium;


Background and aims: The gastroprokinetic activities of ghrelin, the natural ligand of the growth hormone secretagogue receptor (GHS-R), prompted us to compare the effect of ghrelin with that of synthetic peptide (growth hormone releasing peptide 6 (GHRP-6)) and non-peptide (capromorelin) GHS-R agonists both in vivo and in vitro.

Methods: In vivo, the dose dependent effects (1–150 nmol/kg) of ghrelin, GHRP-6, and capromorelin on gastric emptying were measured by the 14C octanoic breath test which was adapted for use in mice. The effect of atropine, NG-nitro-L-arginine methyl ester hydrochloride (l-NAME), or D-Lys3-GHRP-6 (GHS-R antagonist) on the gastroprokinetic effect of capromorelin was also investigated. In vitro, the effect of the GHS-R agonists (1 µM) on electrical field stimulation (EFS) induced responses was studied in fundic strips in the absence and presence of L-NAME.

Results: Ghrelin, GHRP-6, and capromorelin accelerated gastric emptying in an equipotent manner, with bell-shaped dose-response relationships. In the presence of atropine or l-NAME, which delayed gastric emptying, capromorelin failed to accelerate gastric emptying. D-Lys3-GHRP-6 also delayed gastric emptying but did not effectively block the action of the GHS-R agonists, but this may be related to interactions with other receptors. EFS of fundic strips caused frequency dependent relaxations that were not modified by the GHS-R agonists. L-NAME turned EFS induced relaxations into cholinergic contractions that were enhanced by ghrelin, GHRP-6, and capromorelin.

Conclusion: The 14C octanoic breath test is a valuable technique to evaluate drug induced effects on gastric emptying in mice. Peptide and non-peptide GHS-R agonists accelerate gastric emptying of solids in an equipotent manner through activation of GHS receptors, possibly located on local cholinergic enteric nerves.

  • GH, growth hormone
  • GHS, growth hormone secretagogue
  • GHS-R, growth hormone secretagogue receptor
  • GHRP-6, growth hormone releasing peptide 6
  • l-NAME, NG-nitro-l-arginine methyl ester hydrochloride
  • EFS, electrical field stimulation
  • ghrelin
  • gastric emptying
  • breath test
  • organ bath
  • electrical field stimulation

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  • * Dr T Kitazawa is associate professor at the Rakuno Gakuen University in Ebetsu, Hokkaido, Japan, and performed this work during a sabbatical leave in Belgium.

  • Published online first 20 April 2005

  • Conflict of interest: None declared.

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