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

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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 GTPγS 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 μM 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; Pn=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‐HT4 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 μM) 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.British Journal of Pharmacology (2007) 150, 58–64. doi:10.1038/sj.bjp.0706969

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