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  • Title: Characterization of [3H]cholecystokinin octapeptide binding to mouse brain synaptosomes: effects of neuroleptics.
    Author: Hama Y, Ebadi M.
    Journal: Neurochem Res; 1987 Aug; 12(8):729-37. PubMed ID: 3627361.
    Abstract:
    The presence of high concentrations of both dopamine and cholecystokinin (CCK) in the striatum and in various limbic structures suggests that the CCK may not only influence dopaminergic transmission, but it also may be relevant to the psychopathology of schizophrenia and to the therapeutic effects of neuroleptics. By using a synaptosomal fraction isolated from the mouse cerebral cortex and [propionyl-3H]CCK8-sulphate ([3H]CCK8S) as a ligand, a single binding site for [3H]CCK8 with a KD value of 1.04 nM and a Bmax value of 42.9 fmol/mg protein was identified. The competitive inhibition of [3H]CCK8S binding by related peptides produced an order of potency of CCK8-sulphated (IC50 = 5.4 nM) greater than CCK8-unsulfated (IC50 = 40 nM) and greater than CCK4 (IC50 = 125 nM). The regional distribution of [3H]CCK8S binding in the mouse brain was highest in the olfactory bulb (34.3 +/- 5.6 fmol/mg protein) greater than cerebral cortex greater than cerebellum greater than olfactory tubercle greater than striatum greater than pons-medulla greater than mid brain greater than hippocampus greater than hypothalamus (12.4 +/- 2.1 fmol/mg protein). The repeated administration of haloperidol (2.5 mg/kg/tid) increased the binding of [3H]CCK8S in cerebral cortex from 31.8 +/- 1.7 to 38.9 +/- 5.2 fmol/mg protein. The varied distribution of CCK8S receptors may signify nonuniform functions for the octapeptide in the brain.
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