Journal article
Enhanced Gastrointestinal Motility with Orally Active Ghrelin Receptor Agonists
The Journal of pharmacology and experimental therapeutics, v 329(3), pp 1178-1186
01 Jun 2009
PMID: 19252061
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The orexigenic peptide ghrelin has been shown to have prokinetic activity in the gastrointestinal (GI) system of several species, including humans. In this series of experiments, we have evaluated the prokinetic activity of novel, small-molecule ghrelin receptor (GhrR) agonists after parenteral and peroral dosing in mice and rats. Gastric emptying, small intestinal transport, and fecal output were determined after intraperitoneal and intracerebroventricular dosing of GhrR agonists, using ghrelin as a positive control. These same parameters were evaluated after oral gavage dosing of the synthetic agonists. Regardless of dose route, GhrR agonist treatment increased gastric emptying, small intestinal transit, and fecal output. However, fecal output was only increased by GhrR agonist treatment if mice were able to feed during the stimulatory period. Thus, GhrR agonists can stimulate upper GI motility, and the orexigenic action of the compounds can indirectly contribute to prokinetic activity along the entire GI tract. The orexigenic and prokinetic effects of either ghrelin or small-molecule GhrR agonists were selective for the GhrR because they were absent when evaluated in GhrR knockout mice. We next evaluated the efficacy of the synthetic GhrR agonists dosed in a model of opiate-induced bowel dysfunction induced by a single injection of morphine. Oral dosing of a GhrR agonist normalized GI motility in opiate-induced dysmotility. These data demonstrate the potential utility of GhrR agonists for treating gastrointestinal hypomotility disorders.
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Details
- Title
- Enhanced Gastrointestinal Motility with Orally Active Ghrelin Receptor Agonists
- Creators
- Soratree Charoenthongtrakul - Elixir MedicalDerek Giuliana - ELIXIRKenneth A. Longo - ELIXIRElizabeth K. Govek - ELIXIRAnna Nolan - ELIXIRSamantha Gagne - ELIXIRKristen Morgan - ELIXIRJeffrey Hixon - ELIXIRNeil Flynn - Bristol-Myers SquibbBrian J. Murphy - Bristol-Myers SquibbAndres S. Hernandez - Bristol-Myers SquibbJun Li - Bristol-Myers SquibbJoseph A. Tino - Bristol-Myers SquibbDavid A. Gordon - Bristol-Myers SquibbPeter S. DiStefano - ELIXIRBrad J. Geddes - ELIXIR
- Publication Details
- The Journal of pharmacology and experimental therapeutics, v 329(3), pp 1178-1186
- Publisher
- Amer Soc Pharmacology Experimental Therapeutics
- Number of pages
- 9
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000266207800039
- Scopus ID
- 2-s2.0-66749111412
- Other Identifier
- 991021902519004721
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- Web of Science research areas
- Pharmacology & Pharmacy