Ghrelin increases vagally mediated gastric activity by central sites of action

Abstract

Background Vagally dependent gastric reflexes are mediated through vagal afferent fibers synapsing upon neurons of the nucleus tractus solitarius (NTS) which, in turn modulate the preganglionic parasympathetic dorsal motor nucleus of the vagus (DMV) neurons within the medullary dorsal vagal complex (DVC). The expression and transport of ghrelin receptors has been documented for the afferent vagus nerve, and functional studies have confirmed that vagal pathways are integral to ghrelin-induced stimulation of gastric motility. However, the central actions of ghrelin within the DVC have not been explored fully. Methods We assessed the responses to ghrelin in fasted rats using: 1) in vivo measurements of gastric tone and motility following IVth ventricle application or unilateral microinjection of ghrelin into the dorsal vagal complex (DVC); and, 2) whole cell recordings from gastric-projecting neurons of the dorsal motor nucleus of the vagus (DMV) Results 1) IVth ventricle application or unilateral microinjection of ghrelin into the DVC elicited contractions of the gastric corpus via excitation of a vagal cholinergic efferent pathway; 2) Ghrelin facilitates excitatory, but not inhibitory, presynaptic transmission to DMV neurons. Conclusions Our data indicate that ghrelin acts centrally by activating excitatory synaptic inputs onto DMV neurons, resulting in increased cholinergic drive by way of vagal motor innervation to the stomach.

Advances in the physiology of gastric emptying

“…Suppression of NTS‐CC neurons leads to inhibition of the DMV‐C‐i and disinhibition of DMV‐C‐e neurons. Ghrelin also disinhibits DMV‐C‐e neurons by activating AP‐GABA neurons and facilitates excitatory transmission to DMV‐C‐e neurons . Moreover, ghrelin also directly stimulates MY‐C‐e neurons.…”

“…In vivo, ghrelin increases gastric myoelectrical activity and gastric emptying in the rats . Ghrelin activates phase II activity in the antrum of the fasting stomach by a central action . The peripheral action of ghrelin facilitates motilin to induce the activity in front of the MMC .…”

Is Ghrelin Synthesized in the Central Nervous System?

“…In humans, ghrelin regulates some functions that depend on the activity of the autonomic nervous system; for instance, ghrelin increases gastric emptying and decreases blood pressure [28,29,30]. GHSR-1a is expressed in all three components of the dorsal vagal complex, and central administration of ghrelin to rodents recapitulates some of these actions of the hormone [31,32,33]; however, the extent to which these effects of ghrelin depend on its action at central level in humans is currently uncertain. Finally, it is interesting to stress that studies in rodents have shown that ghrelin system also impacts on higher cognitive functions, such as learning and memory, but the implications of these studies in humans are currently unclear [34,35].…”

Brain neuropeptides in gastric mucosal protection

“…In contrast, ghrelin inhibits ischemia/reperfusion-induced mucosal lesions given i.c.v., but increases gastric acid secretion in the same dose range [22]. Moreover, ghrelin injected into the IVth ventricle or into the DVC elicited contractions of the gastric corpus via excitation of a vagal cholinergic efferent pathway [37], however, ghrelin-induced gastroprotective effect was not reduced in higher dose range. The above data suggest the lack of a definitive correlation between the declined gastroprotective effect and the increased gastric acid secretion or gastric motor activity.…”