Alterations in brain cholecystokinin receptors after fasting

Abstract

Cholecystokinin (CCK) is the parent molecule of a family of polypeptide hormones, some of which are secreted from the small intestine after food ingestion and stimulate both exocrine secretion and gall bladder contraction^1–4. CCK-like molecules have also been identified in the central and peripheral nervous systems^5–12. The significance of CCK in the brain is unknown, but it could mediate satiety. The satiety produced by introduction of food into the intestine¹³ can be mimicked by systemic injections of CCK and its analogues^14–17 —these hormones are also effective when injected into the hypothalamus¹⁸ and the cerebral ventricle¹⁹. Straus and Yalow showed that brain CCK levels were reduced in the cerebral cortex of both genetically obese (ob/ob)²⁰ and normal mice after a 2–5-day fast²¹. However, Schneider²² detected no such reduction in similar conditions and other studies have suggested a peripheral rather than central action on satiety^23,24. Using CCK of high specific activity, specific CCK receptors have been measured both in pancreatic acini and in various brain regions^25–28. We show here that fasting in mice significantly increases CCK binding due to an increased number of CCK receptors in the olfactory bulb and hypothalamus, but not in other brain regions. In contrast, insulin binding to its receptors was not altered by fasting. As the hypothalamus is known to regulate appetite^29,30, this finding supports the concept that CCK regulates satiety through interaction with this brain region.