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

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 GTP gamma S 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 I mu M 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-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 mu M) 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.