title: Little or no ability of obestatin to interact with ghrelin or modify motility in the rat gastrointestinal tract.
abstract: 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.
authors.affiliation: Neurology & Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow CM19 5AW, UK.
authors.forename: A K
authors.initials: AK
authors.lastname: Bassil
authors.forename: Y
authors.initials: Y
authors.lastname: Häglund
authors.forename: J
authors.initials: J
authors.lastname: Brown
authors.forename: T
authors.initials: T
authors.lastname: Rudholm
authors.forename: P M
authors.initials: PM
authors.lastname: Hellström
authors.forename: E
authors.initials: E
authors.lastname: Näslund
authors.forename: K
authors.initials: K
authors.lastname: Lee
authors.forename: G J
authors.initials: GJ
authors.lastname: Sanger
mesh_terms: 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
chemical_list: D054439:Ghrelin; D036361:Peptide Hormones; C505799:obestatin, human; D016244:Guanosine 5'-O-(3-Thiotriphosphate)