QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.108.149211v1 329/3/1110    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Venkova, K. Articles by Meerveld, B. G.-V. PubMed PubMed Citation Articles by Venkova, K. Articles by Meerveld, B. G.-V.

GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Efficacy of Ipamorelin, a Novel Ghrelin Mimetic, in a Rodent Model of Postoperative Ileus

Department of Physiology (K.V., B.G.-V.M.), Oklahoma Center for Neuroscience University of Oklahoma Health Science Center (K.V., B.G.-V.M.), and Veterans Administration Medical Center (B.G.-V.M.), Oklahoma City, Oklahoma; and Sapphire Therapeutics, Inc., Bridgewater, New Jersey (W.M., R.N.)

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 µg/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 µg/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.

Address correspondence to: Dr. Beverley Greenwood-Van Meerveld, Veterans Adminsistration Medical Center, Research Administration Rm. 151, 921 NE 13th Street, Oklahoma City, OK 73104. E-mail: beverley-greenwood{at}ouhsc.edu