Attenuated satiation response to intestinal nutrients in rats that do not express CCK-A receptors

Pharmacological experiments suggest that satiation associated with intestin al infusion of several nutrients is mediated by CCK-A receptors. Otsuka Lon g-Evans Tokushima Fatty, (OLETF), rats do not express CCK-A receptors and a re insensitive to the satiation-producing effects of exogenous CCK. To furt her evaluate the role of CCK-A receptors in satiation by intestinal nutrien t infusion, we examined intake of solid (pelleted rat chow) or liquid (12.5 % glucose) food intake, following intestinal infusions of fats (oleic acid or fat emulsion), sugars (maltotriose or glucose), or peptone in OLETF rats and Long Evans Tokushima Orsuka control rats (LETO). Intestinal infusion o f glucose or maltotriose reduced solid food intake more in LETO than in OLE TF rats from 30 min through 4 h post infusion. Reduction of solid food inta ke by intestinal infusions of fat or peptone did not differ between OLETF a nd LETO rats during the first 30 min post infusion, but reduction of intake by these infusates was attenuated in OLETF rats over the ensuing 4h post i nfusion. Intestinal infusion of glucose, oleate, fat emulsion and peptone r educed 30-min intake of 12.5% glucose more in LETO than OLETF rats. Further more, pretreatment with the CCK-A receptor antagonist, devazepide, attenuat ed intestinal nutrient-induced reduction of food intake only in LETO, but n ut OLETF rats. Our results confirm pharmacological results, indicating that CCK-A receptors participate in satiation by nutrients that elevate plasma CCK concentrations, as well as by nutrients that do not stimulate secretion of endocrine CCK. In addition, our results indicate: 1) that OLETF rats ha ve deficits in the satiation response to a variety of intestinal nutrient i nfusions; 2) that the temporal pattern for CCK-A receptor participation in satiation by intestinal nutrients is different during ingestion of liquid a nd solid feuds and 3) that intestinal nutrients provide some satiation sign als that are CCK-A receptor mediated and some that are not. (C) 2001 Elsevi er Science Inc. All rights reserved.