Plasma ghrelin is increased following gastrin stimulation

Abstract

Background: Ghrelin is primarily secreted from the gastric mucosa and has been shown to increase appetite and weight in humans. Plasma concentrations are increased pre-meals but reduced in the fed state. We therefore examined the effects of gastrin stimulation on peripheral plasma ghrelin concentrations in normal human subjects. Methods: Eight normal, H. pylori-negative volunteers (4 male; mean age 26.9 (21–54) years) were studied. Ethical approval for this study was granted by the Ethical Committee of Queen's University of Belfast. Each underwent basal and maximal acid secretory studies before, on completion, and 28 days following a 28-day course of the proton pump inhibitor, esomeprazole 40mg daily. For each acid secretory test, basal blood samples were collected 50 and 40 minutes prior to commencing a 60-minute intravenous infusion of pentagastrin (0.6µg/kg/hr) with further blood sampling at 45, 90 and 240 minutes after commencing the infusion. Plasma gastrin and ghrelin concentrations were assessed by radioimmunoassay. Statistical analysis employed the Wilcoxon Signed Ranks test. Results: Plasma ghrelin was increased by pentagastrin infusion before (p<0.01), on completion (p<0.05) and 28 days following (p<0.01) esomeprazole (165.2 to 220.1 pmol/l, 237.7 to 266.5 pmol/l, 181.9 to 201.0 pmol/l, respectively). The ghrelin increase occurred at 45min and remained elevated at 240min in all three studies. Mean basal plasma gastrin and ghrelin was also increased (25.0ng/l to 51.3 ng/l (p<0.05) and 165.2 pmol/l to 237.7 pmol/l (p<0.01) respectively) following 28 days of esomeprazole. By day-28 post-esomeprazole, both plasma gastrin and ghrelin concentrations had returned to pre-treatment values. Conclusions: Plasma ghrelin was significantly increased by infusion of pentagastrin at a dose inducing maximal gastric acid secretion. This increase occurs immediately and may imply linkage with ECL cell histamine release. Treatment with esomeprazole also causes a significant rise in plasma ghrelin probably by causing an endogenous hypergastrinaemia. This study demonstrates that gastrin plays a key role in ghrelin activity and release. It also demonstrates that the mode of cellular communication amongst oxyntic and antral endocrine cell types requires further examination and additional evaluation of pharmacological intervention is necessary. Acknowledgements: PM Lynch was supported by a United Hospitals Trust Clinical Research Fellowship.