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American Journal of Clinical Nutrition, Vol 55, 286S-290S, Copyright © 1992 by The American Society for Clinical Nutrition, Inc

ORIGINAL RESEARCH COMMUNICATIONS

Potent and sustained satiety actions of a cholecystokinin octapeptide analogue

TH Moran, TK Sawyer, DH Seeb, PJ Ameglio, MA Lombard and PR McHugh
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205.

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.


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Copyright © 1992 by The American Society for Nutrition