CCK-58 elicits both satiety and satiation in rats while CCK-8 elicits only satiation.
Reduction of food intake by exogenous cholecystokinin (CCK) has been demonstrated primarily for its short molecular form, CCK-8. Mounting evidence, however, implicates CCK-58 as a major physiologically active CCK form, with different neural and exocrine response profiles than CCK-8. In three studies, we compared meal-pattern effects of intraperitoneal injections CCK-8 vs. CCK-58 in undeprived male Sprague-Dawley rats consuming sweetened condensed milk. In study 1, rats (N=10) received CCK-8, CCK-58 (0.45, 0.9, 1.8 and 3.6 nmol/kg) or vehicle before a 4-h test-food presentation. At most doses, both CCK-8 and CCK-58 similarly reduced meal size relative to vehicle. Meal-size reduction prompted a compensatory shortening of the intermeal interval (IMI) after CCK-8, but not after CCK-58, which uniquely increased the satiety ratio (IMI/size of the preceding meal). In the second study, lick patterns were monitored after administration of 0.9 nmol/kg CCK-58, CCK-8 or vehicle. Lick cluster size, lick efficiency and interlick-interval distribution remained unaltered compared to vehicle, implying natural satiation, rather than illness, following both CCK forms. In study 3, threshold satiating doses of the two CCK forms were given at 5 and 30 min after meal termination, respectively. CCK 58, but not CCK-8 increased the intermeal interval and satiety ratio compared to vehicle. In conclusion, while CCK 58 and CCK-8 both stimulate satiation, thereby reducing meal size, CCK-58 consistently exerts a satiety effect, prolonging IMI. Given the physiological prominence of CCK-58, these results suggest that CCK's role in food intake regulation may require re-examination.
Weill Medical College, Cornell University, White Plains, NY 10605, USA; Veterans Administration Puget Sound Health Care System, Office of Research and Development Medical Research Service, Seattle, WA 98108, USA; Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA.
Joost
J
Overduin
Weill Medical College, Cornell University, White Plains, NY 10605, USA.
James
J
Gibbs
Veterans Administration Puget Sound Health Care System, Office of Research and Development Medical Research Service, Seattle, WA 98108, USA; Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA.
David E
DE
Cummings
Division of Digestive Diseases, David Geffen School of Medicine at UCLA and CURE: Digestive Diseases Research Center, Veterans Administration, Los Angeles, CA 90073, USA. Electronic address: jreeve@mednet.ucla.edu.
Joseph R
JR
Reeve
D000818:Animals; D002766:Cholecystokinin / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D062407:Meals; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D012527:Satiation / Q000187:drug effects*; D012528:Satiety Response / Q000187:drug effects*
D010446:Peptide Fragments; C410885:cholecystokinin 8; C038823:cholecystokinin 58; D002766:Cholecystokinin
CCK-58; Intermeal interval; Lick microstructure; Meal pattern; Satiety