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1 Physiological Laboratory, School of Biomedical Sciences, University of Liverpool, Liverpool, United Kingdom
2 Department of Gastroenterology, Hope Hospital, University of Manchester, Manchester, United Kingdom
* To whom correspondence should be addressed. E-mail: g.j.dockray{at}liverpool.ac.uk.
Intact vagal afferent neurons are required for the satiety effects of the intestinal hormone cholecystokinin and the orexigenic effects of the gastric regulatory peptide ghrelin. In this study we examined the localisation of ghrelin receptors in nodose ganglia and their function in regulating expression of other orexigenic receptors, notably the cannabinoid (CB)-1 and melanin concentrating hormone (MCH)-1 receptors. Using RT-PCR, transcripts corresponding to both functional (GHS-R1a) and truncated forms (GHS-R1b) of the ghrelin receptor were detected in rat nodose ganglia. There was no difference in expression between rats fed ad libitum or fasted up to 48hr. Immunohistochemical studies using antibodies directed at GHS-R1a revealed expression in over 75% of neurons also expressing CCK-1 receptors in the mid- and caudal regions of the ganglion. There was also expression in human nodose ganglia. In fasted rats in which CB-1 and MCH-1 receptor expression was increased, administration of ghrelin prevented the down regulation by refeeding. We conclude that the actions of CCK and ghrelin are mediated by a common population of vagal-afferent neurons. Ghrelin may act to limit the action of CCK in depressing expression of the CB-1 and MCH-1 receptors other receptors.
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