Potent and sustained satiety actions of a cholecystokinin octapeptide analogue.
The relative ability of a norleucine substituted cholecystokinin (CCK) analogue, U-67827E, to interact with CCK receptors and to inhibit food intake was examined across a variety of paradigms. U-67827E and CCK had identical in vitro potencies as demonstrated by their ability to induce pyloric contractions or competitively inhibit [125I]CCK-8 binding to type A and B CCK receptors. However, the in vivo potency of U-67827E was significantly greater than that of CCK-8. In rats, U-67827E inhibited food intake with 10-100 times the potency of CCK. In rhesus monkeys, U-67827E produced significantly greater inhibitions of daily food intake and did so in a dose-dependent manner with no evidence of compensation or tolerance. U-67827E also inhibited gastric emptying for significantly longer durations than CCK. Together these results demonstrate that CCK analogues with increased in vivo bioavailability can affect food intake beyond a single meal.
Moran
T H
TH
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Sawyer
T K
TK
Seeb
D H
DH
Ameglio
P J
PJ
Lombard
M A
MA
McHugh
P R
PR
D000818:Animals; D002766:Cholecystokinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004435:Eating / Q000187:drug effects; D005746:Gastric Emptying / Q000187:drug effects; D007700:Kinetics; D008253:Macaca mulatta; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000187:drug effects / Q000502:physiology; D012527:Satiation / Q000187:drug effects*; D012844:Sincalide / Q000378:metabolism / Q000494:pharmacology
D011949:Receptors, Cholecystokinin; C060660:U 67827E; D002766:Cholecystokinin; D012844:Sincalide