Minireview. The ascent of cholecystokinin (CCK) - from gut to brain.

Abstract Cholecystokinin (CCK), a classical gastrointestinal polypeptide hormone, appears to have an equally important role as a brain neurotransmitter. CCK is widely distributed throughout both the central and peripheral nervous system. Of the known brain peptides, only CCK and VIP are predominately cerebral cortical peptides. In the pituitary, CCK is found in the posterior pituitary, while gastrin-like peptides are present in the anterior and intermediate lobes. Phylogenetically, gastrin-CCK-like peptides arose extremely early in evolution being present in the primitive nerve cells of the coelenterate, Hydra. Specific high affinity CCK-receptors have been demonstrated in rat and guinea-pig brains with highest concentrations in the cerebral cortex, caudate nucleus and olfactory bulb. Alterations in CCK binding have been reported during fasting and in genetically obese rats and mice. The low levels of CCK receptors in patients with Huntington's Chorea, the coexistance of CCK with dopamine in the same mesolimbic neurons and the rotational syndrome produced after central administration in rats suggests a potential physiological role for CCK in the regulation of extra-pyramidal function. CCK and/or gastrin have been demonstrated to have a number of effects on anterior pituitary hormones and the high concentrations in the posterior pituitary suggest a possible neuromodulatory role in the regulation of vasopressin and/or oxytocin release. CCK is a putative satiety hormone which appears to produce satiety both by peripheral and central effects. The presence of CCK in the periaqueductal gray and the fact that it produces naloxone reversible analgesia suggest a potential role for CCK in the regulation of pain perception. Central administration of CCK produces hyperglycemia which appears to be partly mediated via an adrenal mechanism. CCK also produces mild hypothermia and appears to be a central nervous system depressant. Present evidence indicating that CCK is a central neurotransmitter or neuromodulator includes its regional distribution with localization within neuronal cell bodies and axons; the demonstration that it can be synthesized in neuronal tissue; the fact that it is released by depolarizing stimuli in vitro ; the presence of specific, high affinity receptors for CCK in the brain; and the finding that it can activate isolated neurons. The high concentrations of CCK in the cerebral cortex suggest that future studies will produce further surprises concerning the physiological role of this gall-bladder contracting hormone which came of age with the discovery of its wide distribution in the central nervous system.

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