Efficacy of ipamorelin, a novel ghrelin mimetic, in a rodent model of postoperative ileus.
Ghrelin and ghrelin mimetics stimulate appetite and enhance gastric motility. The present study investigates whether ipamorelin, a selective growth hormone secretagogue and agonist of the ghrelin receptor, would accelerate gastrointestinal transit and ameliorate the symptoms in a rodent model of postoperative ileus (POI). Fasted male rats were subjected to laparotomy and intestinal manipulation. At the end of surgery, a dye marker was infused in the proximal colon to evaluate postsurgical colonic transit time, which was the time to the first bowel movement. In addition, fecal pellet output, food intake, and body weight were monitored regularly for 48 h. Ipamorelin (0.01-1 mg/kg), growth hormone-releasing peptide (GHRP)-6 (20 microg/kg), or vehicle (saline) were administered via intravenous bolus infusion after a single dosing or a 2-day repetitive dosing regimen (four doses a day at 3-h intervals). Compared with the vehicle, a single dose of ipamorelin (1 mg/kg) or GHRP-6 (20 microg/kg) decreased the time to the first bowel movement but had no effect on cumulative fecal output, food intake, or body weight gain measured 48 h after the surgery. In contrast, repetitive dosing of ipamorelin (0.1 or 1 mg/kg) significantly increased the cumulative fecal pellet output, food intake, and body weight gain. The results suggest that postsurgical intravenous infusions of ipamorelin may ameliorate the symptoms in patients with POI.
Venkova
Kalina
K
Department of Physiology, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA.
Mann
William
W
Nelson
Richard
R
Greenwood-Van Meerveld
Beverley
B
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003672:Defecation / Q000187:drug effects; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects; D005765:Gastrointestinal Agents / Q000494:pharmacology / Q000627:therapeutic use; D005772:Gastrointestinal Transit / Q000187:drug effects; D054439:Ghrelin / Q000819:agonists*; D045823:Ileus / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D054440:Receptors, Ghrelin / Q000819:agonists
D005765:Gastrointestinal Agents; D054439:Ghrelin; D009842:Oligopeptides; D054440:Receptors, Ghrelin; C041048:growth hormone releasing hexapeptide; C114611:ipamorelin