title: CCK-58 prolongs the intermeal interval, whereas CCK-8 reduces this interval: not all forms of cholecystokinin have equal bioactivity.
abstract: It has been accepted for decades that "all forms of cholecystokinin (CCK) have equal bioactivity," despite accumulating evidence to the contrary. To challenge this concept, we compared two feeding responses, meal size (MS, 10% sucrose) and intermeal interval (IMI), in response to CCK-58, which is the major endocrine form of CCK, and CCK-8, which is the most abundantly utilized form. Doses (0, 0.1, 0.5, 0.75, 1, 3 and 5 nmol/kg) were administered intraperitoneally over a 210-min test to Sprague Dawley rats that had been food-deprived overnight. We found that (1) all doses of CCK-58, except the lowest dose, and all doses of CCK-8, except the lowest two doses, reduced food intake more than vehicle did; (2) at two doses, 0.75 and 3 nmol/kg, CCK-58 increased the IMI, while CCK-8 failed to alter this feeding response; and (3) CCK-58, at all but the lowest two doses, increased the satiety ratio (IMI between first and second meals (min) divided by first MS (ml)) relative to vehicle, while CCK-8 did not affect this value. These findings demonstrate that the only circulating form of CCK in rats, CCK-58, prolongs the IMI more than CCK-8, the peptide generally utilized in feeding studies. Taken together, these results add to a growing list of functions where CCK-8 and CCK-58 express qualitatively different bioactivities. In conclusion, the hypothesis that "all forms of cholecystokinin (CCK) have equal bioactivity" is not supported.
authors.affiliation: Gastroenterology Laboratory, Department of Biomedical Sciences, College of Veterinary Medicine, Tuskegee University, Tuskegee, AL, United States. Electronic address: sayeghai@mytu.tuskegee.edu.
authors.forename: Ayman I
authors.initials: AI
authors.lastname: Sayegh
authors.affiliation: Gastroenterology Laboratory, Department of Biomedical Sciences, College of Veterinary Medicine, Tuskegee University, Tuskegee, AL, United States.
authors.forename: Martha C
authors.initials: MC
authors.lastname: Washington
authors.affiliation: Gastroenterology Laboratory, Department of Biomedical Sciences, College of Veterinary Medicine, Tuskegee University, Tuskegee, AL, United States.
authors.forename: Shannon J
authors.initials: SJ
authors.lastname: Raboin
authors.affiliation: School of Medicine, Wayne State University, Detroit, MI, United States.
authors.forename: Amnah H
authors.initials: AH
authors.lastname: Aglan
authors.affiliation: CURE: Digestive Diseases Research Center, Veterans Administration Greater Los Angeles Healthcare System, and Digestive Diseases Division, School of Medicine, University of California, Los Angeles, CA, United States.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Reeve
mesh_terms: D000818:Animals; D001066:Appetite / Q000187:drug effects; D001067:Appetite Depressants / Q000494:pharmacology*; D019167:Appetite Stimulants / Q000494:pharmacology*; D002766:Cholecystokinin / Q000494:pharmacology*; D002149:Energy Intake; D005247:Feeding Behavior / Q000187:drug effects; D008297:Male; D017207:Rats, Sprague-Dawley; D012844:Sincalide / Q000494:pharmacology*
chemical_list: D001067:Appetite Depressants; D019167:Appetite Stimulants; C038823:cholecystokinin 58; D002766:Cholecystokinin; D012844:Sincalide
keywords: Cholecystokinin; Intermeal interval; Satiation; Satiety; Satiety ratio