ABSTRACT
We previously demonstrated that a transient surge in plasma levels of ghrelin occurs just prior to a scheduled meal and that this surge is modified by the feeding regimen. This suggests that the ghrelin secretion is regulated by the autonomic nervous system, especially the cholinergic projections to the stomach. To test this hypothesis, we investigated changes in plasma ghrelin levels at feeding time in rams by administering cholinergic blockers (atropine and hexamethonium) and a cholinergic accelerator (metoclopramide). The average food intake in each group infused with atropine, hexamethonium, metoclopramide, and saline was 150+/-28, 137+/-46, 153+/-50, and 1075+/-25g, respectively. Plasma ghrelin concentrations increased (P<0.05) after i.v. infusion of hexamethonium and gradually decreased (P<0.05) after i.v. infusion of metoclopramide. Plasma ghrelin levels in hexamethonium-treated animals were greater (P<0.05) than those of atropine-treated animals. Plasma ghrelin levels were significantly (P<0.05) higher in sheep given i.v. infusions of atropine or hexamethonium than the levels in normal- or pair-fed sheep infused with saline. Plasma ghrelin levels were similar in metoclopramide-treated, pair-fed, and control animals. These results support the possibility that ghrelin secretion is regulated by cholinergic neurons of the vagus and that cholinergic activity suppresses ghrelin secretion in sheep.
Subject(s)
Cholinergic Agents/pharmacology , Eating/physiology , Neurons/physiology , Peptide Hormones/blood , Vagus Nerve/physiology , Animals , Atropine/pharmacology , Cholinergic Agonists/pharmacology , Cholinergic Antagonists/pharmacology , Eating/drug effects , Ghrelin , Hexamethonium/pharmacology , Kinetics , Male , Metoclopramide/pharmacology , Neurons/classification , Peptide Hormones/metabolism , Sheep , Vagus Nerve/cytologyABSTRACT
Ghrelin is a recently identified orexigenic hormone secreted by the stomach and has been implicated in meal-time hunger. Several experiments demonstrate a transient surge in ghrelin secretion shortly before a scheduled meal, suggesting from the involvement of cephalic mechanisms. If ghrelin secretion is stimulated by hunger in sheep, plasma levels of ghrelin should be modified by different feeding regimens that affect hunger drive. To test this hypothesis, we investigated changes in plasma ghrelin concentrations in fed Suffolk rams ad libitum and in rams either twice or four times daily. Plasma ghrelin levels increased (P<0.05) abruptly just before every feeding period in sheep fed twice and four times daily and then fell shortly after feeding. Peak levels of the pre-prandial ghrelin surge were higher (P<0.01) in animals fed twice daily than in animals fed four times daily, leading to greater (P<0.05) areas under response curves over 12h. In contrast, the plasma ghrelin levels remained relatively low and constant in sheep fed ad libitum, with no evidence of surges in plasma ghrelin levels. These results confirm that the transient surge in plasma ghrelin levels occurs just before feeding and demonstrate that this can be modified by the feeding regimen in sheep.
