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This Article Full Text Full Text (PDF) All Versions of this Article: 576/1/329    most recent jphysiol.2006.116160v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Shimizu, Y. Articles by Furness, J. B. Search for Related Content PubMed PubMed Citation Articles by Shimizu, Y. Articles by Furness, J. B. Related Collections Alimentary

¹ Department of Anatomy & Cell Biology and Centre for Neuroscience, University of Melbourne, Parkville, Victoria 3010, Australia
² Department of Basic Veterinary Science, School of Veterinary Sciences, Gifu University, Gifu, Japan
³ Neurology and GI CEDD, GlaxoSmithKline, New Frontiers Science Park, Harlow CM19 5AW, UK

Previous studies have failed to reveal an effect of the gastrointestinal peptide hormone ghrelin on colonic motility. In the present work, ghrelin was applied into the lumbo-sacral spinal cord in the region of defecation control centres, and a synthetic ghrelin receptor agonist, CP464709, which crosses the blood–brain barrier, was applied intravenously or into the lumbo-sacral cord. Both ghrelin and CP464709 elicited propulsive contractions and emptying of the colon in anaesthetized rats. In conscious rats, subcutaneous CP464709 caused fecal expulsion. The sites of action and nerve pathways involved in the stimulation of the colon by ghrelin receptor activation were investigated in anaesthetized rats. Intrathecal application of CP464709 at L6–S1, but not application at ponto-medullary levels or to the thoracic spinal cord, elicited propulsive contractions. The stimulation evoked by intravenous CP464709 was prevented if the pelvic nerve outflows were severed, but not if the spinal cord was cut rostral to the defecation centre at L6–S3. The response was also blocked by hexamethonium. When ghrelin, applied intrathecally, was used to desensitize its receptors, the effect of intravenous CP464709 was blocked. CP464709 did not affect small intestine motility or the amplitudes of visceromotor reflexes caused by colorectal distension. It is concluded that activation of ghrelin receptors in the lumbo-sacral spinal cord triggers co-ordinated propulsive contractions that empty the colo-rectum. The pathways through which these responses are generated pass out of the spinal cord via the pelvic nerves and cause propulsive contractions through activation of enteric neurons.

(Received 28 June 2006; accepted after revision 20 July 2006; first published online 27 July 2006)
Corresponding author J. B. Furness: Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Victoria 3010, Australia. Email: j.furness{at}unimelb.edu.au