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Am J Physiol Endocrinol Metab 295: E1487-E1494, 2008. First published October 28, 2008; doi:10.1152/ajpendo.90791.2008
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Dose-dependent effects of cholecystokinin-8 on antropyloroduodenal motility, gastrointestinal hormones, appetite, and energy intake in healthy men

Ixchel M. Brennan,1,2 Tanya J. Little,1 Kate L. Feltrin,1 Andre J. P. M. Smout,3 Judith M. Wishart,1,2 Michael Horowitz,1,2 and Christine Feinle-Bisset1,2

1University of Adelaide Discipline of Medicine and 2National Health and Medical Research Council of Australia Centre of Clinical Research Excellence in Nutritional Physiology, Interventions, and Outcomes, Adelaide, South Australia, Australia; and 3Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands

Submitted 25 September 2008 ; accepted in final form 22 October 2008

CCK mediates the effects of nutrients on gastrointestinal motility and appetite. Intravenously administered CCK stimulates pyloric pressures, increases plasma PYY, and suppresses ghrelin, all of which may be important in the regulation of appetite and energy intake. The dose-related effects of exogenous CCK on gastrointestinal motility and gut hormone release, and the relationships between these effects and those on energy intake, are uncertain. We hypothesized that 1) intravenous CCK-8 would have dose-dependent effects on antropyloroduodenal (APD) pressures, plasma PYY and ghrelin concentrations, appetite, and energy intake and 2) the suppression of energy intake by CCK-8 would be related to the stimulation of pyloric motility. Ten healthy men (age 26 ± 2 yr) were studied on four separate occasions in double-blind, randomized fashion. APD pressures, plasma PYY and ghrelin, and appetite were measured during 120-min intravenous infusions of 1) saline ("control") or 2) CCK-8 at 0.33 ("CCK0.33"), 3) 0.66 ("CCK0.66"), or 4) 2.0 ("CCK2.0") ng·kg–1·min–1. After 90 min, energy intake at a buffet meal was quantified. CCK-8 dose-dependently stimulated phasic and tonic pyloric pressures and plasma PYY concentrations (r > 0.70, P < 0.05) and reduced desire to eat and energy intake (r > –0.60, P < 0.05) without inducing nausea. There were relationships between basal pyloric pressure and isolated pyloric pressure waves (IPPW) with plasma CCK (r > 0.50, P < 0.01) and between energy intake with IPPW (r = –0.70, P < 0.05). Therefore, our study demonstrates that exogenous CCK-8 has dose-related effects on APD motility, plasma PYY, desire to eat, and energy intake and suggests that the suppression of energy intake is related to the stimulation of IPPW.

gut motility; gastrointestinal peptides



Address for correspondence: C. Feinle-Bisset, Univ. of Adelaide Discipline of Medicine, Royal Adelaide Hospital, North Terrace, Adelaide, SA 5000 Australia (e-mail: christine.feinle{at}adelaide.edu.au)







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