Acetylcholine regulates ghrelin secretion in humans.
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 microg(*)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 (11290.5 +/- 6688.7 pg(*)min/ml; P < 0.05) and reduced by PZ (-23205.0 +/- 8959.5 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.
Broglio
Fabio
F
Department of Internal Medicine, Erasmus University of Rotterdam, Rotterdam 3015, The Netherlands.
Gottero
Cristina
C
Van Koetsveld
Peter
P
Prodam
Flavia
F
Destefanis
Silvia
S
Benso
Andrea
A
Gauna
Carlotta
C
Hofland
Leo
L
Arvat
Emanuela
E
van der Lely
Aart Jan
AJ
Ghigo
Ezio
E
D000109:Acetylcholine / Q000502:physiology*; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D054439:Ghrelin; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D036361:Peptide Hormones / Q000097:blood / Q000378:metabolism*; D010890:Pirenzepine / Q000494:pharmacology; D011729:Pyridostigmine Bromide / Q000494:pharmacology
D001786:Blood Glucose; D002800:Cholinesterase Inhibitors; D054439:Ghrelin; D007328:Insulin; D018727:Muscarinic Antagonists; D036361:Peptide Hormones; D019382:Human Growth Hormone; D010890:Pirenzepine; D011729:Pyridostigmine Bromide; D000109:Acetylcholine