Prokinetic effects of a new ghrelin receptor agonist TZP-101 in a rat model of postoperative ileus.
Postoperative ileus (POI) is a major cause of postoperative complications and prolonged hospitalization. Ghrelin, which is the endogenous ligand for the growth hormone secretagogue receptor, has been found to stimulate gastric motility and accelerate gastric emptying. The present study investigates whether TZP-101 (0.03-1 mg/kg i.v.), a synthetic ghrelin-receptor agonist, could improve gastrointestinal transit in rats with POI. Since the main factors for the development of POI are the surgical manipulation and the gastrointestinal effects of opioid-receptor agonists used for pain management, the effect of TZP-101 was investigated in rats subjected to surgery, to morphine treatment (3 mg/kg s.c.), or to a combination of both. The results showed that TZP-101 is equally effective against the delayed gastrointestinal transit induced by surgery, by morphine, or by the combination of both interventions. The prokinetic action of TZP-101 was more pronounced in the stomach compared to the small intestine.
Venkova
Kalina
K
VA Medical Center, Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma 73104, USA.
Fraser
Graeme
G
Hoveyda
Hamid R
HR
Greenwood-Van Meerveld
Beverley
B
D000701:Analgesics, Opioid / Q000627:therapeutic use; D000818:Animals; D001665:Binding Sites; D004359:Drug Therapy, Combination; D005769:Gastrointestinal Motility / Q000187:drug effects*; D005772:Gastrointestinal Transit / Q000187:drug effects*; D054439:Ghrelin; D045823:Ileus / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D009020:Morphine / Q000627:therapeutic use; D036361:Peptide Hormones / Q000627:therapeutic use*; D011183:Postoperative Complications; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000819:agonists*; D054440:Receptors, Ghrelin; D017450:Receptors, Opioid, mu / Q000187:drug effects; D016896:Treatment Outcome
D000701:Analgesics, Opioid; D054439:Ghrelin; D036361:Peptide Hormones; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D017450:Receptors, Opioid, mu; D009020:Morphine