Ghrelin selectively reduces mechanosensitivity of upper gastrointestinal vagal afferents

Abstract

Ghrelin is a peptide released from gastric endocrine cells that 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 ferret esophagus that 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]-growth hormone-releasing peptide (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.

The glucagon-like peptide-1 analog liraglutide suppresses ghrelin and controls diabetes in a patient with Prader-Willi syndrome

“…On the basis of the data in the previous reports [21][22][23][24][25], it is conceivable that postprandial elevation of plasma active GLP-1 concentration suppresses ghrelin secretion via the vagal nerve system. Nevertheless, a pharmacological amount of GLP-1 was needed to lower plasma ghrelin in the patient with PWS.…”

The Enteric Nervous System and Gastrointestinal Innervation: Integrated Local and Central Control

“…Experiments in which the antral mucosa was separated from the underlying muscle, a procedure that abolishes vago-vagal reflexes, suggest that mucosal mechanoreceptors may discriminate particles by size and regulate their passage into the duodenum [18]. Mucosal afferents may also be involved in the control of satiety, as their mechanosensitivity is enhanced by the satiety hormone, leptin, and reduced by the feeding hormone, ghrelin, both of which are released from gastric enteroendocrine cells that are in close proximity to the gastric mucosal afferent endings [19,20]. In humans, ghrelin signalling to hypothalamic feeding centers is via the vagus [21].…”

Role of Vagus Nerve in Gastroduodenal Adaptation and Cytoprotection

“…Ghrelin, an orexigenic hormone secreted from the stomach, was soon after its discovery hypothesized to be a prokinetic agent, due to its homology to the motilin. Investigation of ghrelin physiology has demonstrated that ghrelin is secreted by gastric endocrine cells into the bloodstream, providing local effects by modulating the information up-flow through the vagus nerve to the brain stem nuclei and hypothalamus [17]. Additionally to this ghrelin may also stimulate the production of growth hormone.…”