Ghrelin augments afferent response to distension in rat isolated jejunum.
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.
Murray
C D R
CD
St Mark's Hospital, Harrow, UK. charlie.murray@talk21.com
Booth
C E
CE
Bulmer
D C E
DC
Kamm
M A
MA
Emmanuel
A V
AV
Winchester
W J
WJ
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*
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