Effect of ghrelin and growth hormone-releasing peptide 6 on septic ileus in mice.
Ghrelin is an orexigenic peptide with prokinetic effects in the rat. We investigated the effect of ghrelin and growth hormone-releasing hormone 6 (GHRP-6) on gastric emptying and transit in control and septic mice. Mice were injected i.p. with lipopolysaccharides (LPS) or saline (control). After 16-17 h mice were pretreated with saline, ghrelin or GHRP-6 1 h before intragastric administration of Evans blue. Fifteen minutes later, after assessment of the behaviour scale, mice were killed and gastric emptying, transit and rectal temperature were measured. In control mice, ghrelin (100 microg kg(-1)) and GHRP-6 (20-100 microg kg(-1)) accelerated gastric emptying, whereas ghrelin and GHRP-6 failed to increase transit significantly. Septic mice developed a delay in gastric emptying and transit, hypothermia and a deterioration of the behaviour scale. In septic mice, ghrelin (20 microg kg(-1)) accelerated gastric emptying without effect on transit while GHRP-6 significantly accelerated gastric emptying dose-dependently and failed to increase transit significantly. Ghrelin and GHRP-6 had no effect on the endotoxin-induced hypothermia or deterioration of behaviour scale. Therefore, the beneficial prokinetic effect of ghrelin but mainly of GHRP-6 offers potential therapeutic options in the treatment of septic gastric ileus.
De Winter
B Y
BY
Division of Gastroenterology, Faculty of Medicine, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium. benedicte.dewinter@ua.ac.be
De Man
J G
JG
Seerden
T C
TC
Depoortere
I
I
Herman
A G
AG
Peeters
T L
TL
Pelckmans
P A
PA
D000818:Animals; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology; D054439:Ghrelin; D045823:Ileus / Q000188:drug therapy* / Q000382:microbiology; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use*; D036361:Peptide Hormones / Q000494:pharmacology / Q000627:therapeutic use*; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology
D054439:Ghrelin; D009842:Oligopeptides; D036361:Peptide Hormones; C041048:growth hormone releasing hexapeptide