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Prokinetic Effects of a New Ghrelin Receptor Agonist TZP-101 in a Rat Model of Postoperative Ileus

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Abstract

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.

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Acknowledgments

This work was supported by Tranzyme Pharma. The authors would like to thank Anthony Johnson for his assistance with the surgery.

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Authors and Affiliations

  1. VA Medical Center, Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, 73104, USA

    Kalina Venkova & Beverley Greenwood-Van Meerveld

  2. Tranzyme Pharma, Sherbrooke, Quebec, J1H 5N4, Canada

    Graeme Fraser & Hamid R. Hoveyda

  3. VA Medical Center, Research Administration RM 151, 921 NE 13th Street, Oklahoma City, Oklahoma, 73104, USA

    Beverley Greenwood-Van Meerveld

Authors
  1. Kalina Venkova
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  2. Graeme Fraser
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  3. Hamid R. Hoveyda
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  4. Beverley Greenwood-Van Meerveld
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Correspondence to Beverley Greenwood-Van Meerveld.

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Venkova, K., Fraser, G., Hoveyda, H.R. et al. Prokinetic Effects of a New Ghrelin Receptor Agonist TZP-101 in a Rat Model of Postoperative Ileus. Dig Dis Sci 52, 2241–2248 (2007). https://doi.org/10.1007/s10620-007-9783-7

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  • DOI: https://doi.org/10.1007/s10620-007-9783-7

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