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Br J Pharmacol. 2007 Jan;150(1):58-64. Epub 2006 Nov 27.

Little or no ability of obestatin to interact with ghrelin or modify motility in the rat gastrointestinal tract.

Author information

1
Neurology & Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow CM19 5AW, UK.

Abstract

BACKGROUND AND PURPOSE:

Obestatin, encoded by the ghrelin gene may inhibit gastrointestinal (GI) motility. This activity was re-investigated.

EXPERIMENTAL APPROACH:

Rat GI motility was studied in vitro (jejunum contractility and cholinergically-mediated contractions of forestomach evoked by electrical field stimulation; EFS) and in vivo (gastric emptying and intestinal myoelectrical activity). Ghrelin receptor function was studied using a GTPgammaS assay and transfected cells.

KEY RESULTS:

Contractions of the jejunum or forestomach were unaffected by obestatin 100 nM or 0.01-1000 nM, respectively (P>0.05 each; n=4-18). Obestatin (0.1-1 nM) reduced the ability of ghrelin 1 microM to facilitate EFS-evoked contractions of the stomach (increases were 42.7+/-7.8% and 21.2+/-5.0 % in the absence and presence of obestatin 1 nM; P<0.05; n=12); higher concentrations (10-1000 nM) tended to reduce the response to ghrelin but changes were not statistically significant. Similar concentrations of obestatin did not significantly reduce a facilitation of contractions caused by the 5-HT(4) receptor agonist prucalopride, although an inhibitory trend occurred at the higher concentrations (increases were 69.3+/-14.0% and 42.6+/-8.7% in the absence and presence of 1000 nM obestatin; n=10). Obestatin (up to 10 microM) did not modulate recombinant ghrelin receptor function. Ghrelin increased gastric emptying and reduced MMC cycle time; obestatin (1000 and 30,000 pmol kg(-1) min(-1)) had no effects. Obestatin (2500 pmol kg(-1) min(-1), starting 10 min before ghrelin) did not prevent the ability of ghrelin (500 pmol kg(-1) min(-1)) to shorten MMC cycle time.

CONCLUSIONS AND IMPLICATIONS:

Obestatin has little ability to modulate rat GI motility.

PMID:
17128285
PMCID:
PMC2013842
DOI:
10.1038/sj.bjp.0706969
[Indexed for MEDLINE]
Free PMC Article

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