Alterations in brain cholecystokinin receptors after fasting

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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 contraction1–4. CCK-like molecules have also been identified in the central and peripheral nervous systems5–12. 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 analogues14–17 —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 satiety23,24. Using CCK of high specific activity, specific CCK receptors have been measured both in pancreatic acini and in various brain regions25–28. 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 appetite29,30, this finding supports the concept that CCK regulates satiety through interaction with this brain region.

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Saito, A., Williams, J. & Goldfine, I. Alterations in brain cholecystokinin receptors after fasting. Nature 289, 599–600 (1981) doi:10.1038/289599a0

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