TITLE

Gastric motor effects of peptide and non-peptide in agonists in mice in vivo and in vitro

AUTHOR(S)
Kitazawa, T; De Smet, B.; Verbeke, K.; Depoortere, I.; Peeters, T. L.
PUB. DATE
August 2005
SOURCE
Gut;Aug2005, Vol. 54 Issue 8, p1078
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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) GNS-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 emplying 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 emplying, 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 ogonists, 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. I 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.
ACCESSION #
17813999

 

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