title: Ghrelin augments afferent response to distension in rat isolated jejunum.
abstract: Ghrelin has been shown to decrease firing of gastric vagal afferents at doses comparable with circulating levels in the fasted state. This raises the possibility that ghrelin may have a hormonal action on other vagal afferent populations. The aim of this study was to determine the effects of ghrelin on jejunal afferent activity; including responses to distension, 2-methyl-5-hydroxytryptamine (2-methyl-5-HT) and cholecystokinin (CCK) in both naïve and vagotomized rats. Ghrelin significantly augmented the afferent response to distension. No effect was observed on baseline afferent discharge, or the response to 2-methyl-5-HT and CCK. The effect of ghrelin was more pronounced at lower ramp distending pressures (0-30 mmHg). Similarly, ghrelin augmented the jejunal afferent responses to phasic distension at 10-30 mmHg, but had no effect at higher pressures. Chronic subdiaphragmatic vagotomy and administration of the growth hormone secretagogue receptor (GHS-R) antagonist [D-Lys3]-GHRP-6 prevented the augmentation of the afferent responses to distension indicating ghrelin is acting through the GHS-R on vagal afferent fibres. Ghrelin augments the mechanosensation of jejunal vagal afferents and hence may lead to increased perception of hunger contractions.
authors.affiliation: St Mark's Hospital, Harrow, UK. charlie.murray@talk21.com
authors.forename: C D R
authors.initials: CD
authors.lastname: Murray
authors.forename: C E
authors.initials: CE
authors.lastname: Booth
authors.forename: D C E
authors.initials: DC
authors.lastname: Bulmer
authors.forename: M A
authors.initials: MA
authors.lastname: Kamm
authors.forename: A V
authors.initials: AV
authors.lastname: Emmanuel
authors.forename: W J
authors.initials: WJ
authors.lastname: Winchester
mesh_terms: D000818:Animals; D002404:Catheterization; D002756:Cholagogues and Choleretics / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology; D003187:Compliance; D004594:Electrophysiology; D054439:Ghrelin; D006815:Hunger / Q000502:physiology; D066298:In Vitro Techniques; D007583:Jejunum / Q000294:innervation* / Q000502:physiology*; D008465:Mechanoreceptors / Q000187:drug effects / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology; D036361:Peptide Hormones / Q000494:pharmacology* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D012965:Sodium Chloride / Q000494:pharmacology; D014628:Vagotomy; D017833:Visceral Afferents / Q000187:drug effects* / Q000502:physiology*
chemical_list: D002756:Cholagogues and Choleretics; D054439:Ghrelin; D009842:Oligopeptides; D036361:Peptide Hormones; D012701:Serotonin; D012965:Sodium Chloride; C041048:growth hormone releasing hexapeptide; C045918:2-methyl-5-HT; D002766:Cholecystokinin