Submitted on November 19, 2006
Accepted on February 1, 2007
Ghrelin selectively reduces mechanosensitivity of upper gastrointestinal vagal afferents
Amanda J. Page1*, James A. Slattery2, Catherine Milte2, Rhianna Laker2, Tracey A O'Donnell3, Camilla Dorian3, Stuart M Brierley3, and L. Ashley Blackshaw4
1 Nerve-Gut Research Laboratory, Department of Gastroenterology, Hepatology and General Medicine, Royal Adelaide Hospital, adelaide, South Australia, Australia; Discipline of Physiology, University of Adelaide, Adelaide, South Australia, Australia; Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia
2 Nerve-Gut Research Laboratory, Department of Gastroenterology, Hepatology and General Medicine, Royal Adelaide Hospital, adelaide, South Australia, Australia; Discipline of Physiology, University of Adelaide, Adelaide, South Australia, Australia
3 Nerve-Gut Research Laboratory, Department of Gastroenterology, Hepatology and General Medicine, Royal Adelaide Hospital, adelaide, South Australia, Australia
4 NerveGut Research Laboratory, Royal Adelaide Hospital, Adelaide SA 5000, Australia; Discipline of Physiology, University of Adelaide, Adelaide, South Australia, Australia; Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia
* To whom correspondence should be addressed. E-mail: apage{at}mail.rah.sa.gov.au.
Ghrelin is a peptide released from gastric endocrine cells which has an orexigenic effect via a vagal pathway. Here we determine the effect of ghrelin on mechanosensitivity of upper-intestinal vagal afferent fibers in ferret and mouse. The responses of gastroesophageal vagal afferents to graded mechanical stimulation were determined in vitro before and during application of ghrelin to their peripheral endings. Three types of vagal afferent were tested: tension receptors responding to circumferential tension, mucosal receptors responding only to mucosal stroking and tension/mucosal (TM) receptors in ferrets which responded to both stimuli. In the mouse, ghrelin did not significantly affect the response of mucosal receptors to mucosal stroking with calibrated von Frey hairs. However, it significantly reduced responses of tension receptors to circumferential tension (p<0.005; two-way ANOVA) by up to 40%. This inhibition was reversed by the ghrelin receptor antagonist [D-Lys-3]-GHRP-6. In the ferret, ghrelin significantly reduced the response of mucosal and TM receptors to mucosal stroking with calibrated von Frey hairs. Surprisingly ghrelin did not significantly alter the response to circumferential tension in either tension or TM receptors. RT-PCR analysis indicated that both ghrelin and its receptor are expressed in vagal afferent cell bodies in mouse nodose ganglia. In conclusion, ghrelin selectively inhibits subpopulations of mechanically sensitive gastroesophageal vagal afferents; there is also potential for ghrelin release from vagal afferents. However, the subpopulation of afferents inhibited differs between species. These data have broad implications for ghrelin's role in food intake regulation and reflex control of gastrointestinal function.
