Submitted on September 25, 2008
Revised on October 22, 2008
Accepted on October 22, 2008
Dose-dependent effects of cholecystokinin-8 on antropyloroduodenal motility, gastrointestinal hormones, appetite and energy intake in healthy men
Ixchel M Brennan1, Tanya J Little2, Kate L Feltrin3, Andre JPM Smout4, Judith Wishart, Michael Horowitz5, and Christine Feinle-Bisset6*
1 University of Adelaide, Royal Adelaide Hospital
2 University of Adelaide, Royal Adelaide Hopsital
3 University of Adelaide Discipline of Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia
4 University Medical Center Utrecht
5 University of Adelaide
6 University of Adelaide Discipline of Medicine and NHMRC Centre of Clinical Research Excellence in Nutritional Physiology, Interventions and Outcomes
* To whom correspondence should be addressed. E-mail: christine.feinle{at}adelaide.edu.au.
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: (i) intravenous CCK-8 would have dose-dependent effects on antropyloroduodenal (APD) pressures, plasma PYY and ghrelin concentrations, appetite and energy intake; and (ii) 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 (i) saline ('control'), or CCK-8 at (ii) 0.33 ('CCK0.33'), (iii) 0.66 ('CCK0.66') or (iv) 2.0 ('CCK2.0') ng/kg/min. 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 (IPPWs) with plasma CCK (r>0.50, P<0.01), and between energy intake with IPPWs (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 IPPWs.
