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Acetylcholine Regulates Ghrelin Secretion in Humans

Division of Endocrinology (F.B., P.V.K., C.Ga., L.H., A.J.v.d.L.), Department of Internal Medicine, Erasmus University of Rotterdam, Rotterdam 3015, The Netherlands; and Division of Endocrinology and Metabolism (F.B., C.Go., F.P., S.D., A.B., E.A., E.G.), Department of Internal Medicine, University of Turin, 10126 Turin, Italy

Address all correspondence and requests for reprints to: E. Ghigo, M.D., Division of Endocrinology, Department of Internal Medicine, University of Turin, c.so Dogliotti, 14, 10126 Torino, Italy. E-mail: ezio.ghigo{at}unito.it.

Ghrelin secretion has been reportedly increased by fasting and energy restriction but decreased by food intake, glucose, insulin, and somatostatin. However, its regulation is still far from clarified. The cholinergic system mediates some ghrelin actions, e.g. stimulation of gastric contractility and acid secretion and its orexigenic activity. To clarify whether ghrelin secretion undergoes cholinergic control in humans, we studied the effects of pirenzepine [PZ, 100 mg per os (by mouth)], a muscarinic antagonist, or pyridostigmine (PD, 120 mg per os), an indirect cholinergic agonist, on ghrelin, GH, insulin, and glucose levels in six normal subjects. PD increased (P < 0.05) GH (change in area under curves, mean ± SEM, 790.9 ± 229.3 µg_*min/liter) but did not modify insulin and glucose levels. PZ did not significantly modify GH, insulin, and glucose levels. Circulating ghrelin levels were increased by PD (11,290.5 ± 6,688.7 pg_*min/ml; P < 0.05) and reduced by PZ (–23,205.0 ± 8,959.5 pg_*min/ml; P < 0.01). The PD-induced ghrelin peak did not precede that of GH. In conclusion, circulating ghrelin levels in humans are increased and reduced by cholinergic agonists and antagonists, respectively. Thus, ghrelin secretion is under cholinergic, namely muscarinic, control in humans. The variations in circulating ghrelin levels induced by PD and PZ are unlikely to mediate the cholinergic influence on GH secretion.

This work was supported by Eureka Project (Peptido 1923), Ministero dell’Università e della Ricerca Scientifica, University of Turin, and Fondazione per lo Studio delle Mulattie Endocrino-Metaboliche. The research activity of F.B. at the Division of Endocrinology and Metabolism of the Erasmus University of Rotterdam is supported by a grant from the GH/IGF-I Society.

Abbreviations: BMI, Body mass index; CV, coefficient(s) of variation; PD, pyridostigmine; PZ, pirenzepine; SS, somatostatin.

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