Little or no ability of obestatin to interact with ghrelin or modify motility in the rat gastrointestinal tract.
OBJECTIVE
Obestatin, encoded by the ghrelin gene may inhibit gastrointestinal (GI) motility. This activity was re-investigated.


METHODS
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.


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
Obestatin has little ability to modulate rat GI motility.
Bassil
A K
AK
Neurology & Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow CM19 5AW, UK.
Häglund
Y
Y
Brown
J
J
Rudholm
T
T
Hellström
P M
PM
Näslund
E
E
Lee
K
K
Sanger
G J
GJ
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005769:Gastrointestinal Motility / Q000187:drug effects*; D041981:Gastrointestinal Tract / Q000187:drug effects* / Q000502:physiology; D054439:Ghrelin; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D066298:In Vitro Techniques; D036361:Peptide Hormones / Q000187:drug effects* / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D054439:Ghrelin; D036361:Peptide Hormones; C505799:obestatin, human; D016244:Guanosine 5'-O-(3-Thiotriphosphate)