CCK and CCK-A receptors in the control of feeding behavior

We investigated the relationship between plasma cholecystokinin (CCK) levels and abnormal eating behavior in patients suffering from anorexia nervosa and in genetically obese and diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Baseline CCK values were significantly increased in anorexic patients compared to those in controls. In control subjects, plasma CCK reached the peak level at 45 min following a test meal ingestion. In anorexic patients, however, a small CCK peak was observed at 20-30 min, followed by a small transient decrease, but thereafter it further increased until the end of the observation. In OLETF rats, plasma CCK levels were significantly high compared to those in the control rats. In contrast to anorexic patients, OLETF rats showed a significantly higher average daily food intake, gained body weight faster and were heavier than the control rats. The exocrine pancreas of OLETF rats were totally and specifically insensitive to endogenous as well as exogenous CCK stimulation. [I-125]CCK-8 binding to acini was totally absent in the OLETF rats. Moreover, the expression of the CCK-A receptor gene could not be detected, whereas the CCK-B receptor gene was observed in the stomach, the pancreas and the brain by the reverse-transcription polymerase chain reaction method. These results demonstrate that CCK and CCK-A receptors have a crucial role not only in the regulation of the gastrointestinal digestion, but also in the control of feeding behavior.