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  • Title: Cholecystokinin-induced protection of cultured cortical neurons against glutamate neurotoxicity.
    Author: Akaike A, Tamura Y, Sato Y, Ozaki K, Matsuoka R, Miura S, Yoshinaga T.
    Journal: Brain Res; 1991 Aug 23; 557(1-2):303-7. PubMed ID: 1684128.
    Abstract:
    The effects of cholecystokinin (CCK) on glutamate-induced neurotoxicity were examined using cultured rat cortical neurons. Brief exposure of glutamate followed by an incubation with normal solution for more than 60 min reduced cell viability by 60-70%, compared with control values. Glutamate-induced neurotoxicity was significantly inhibited by MK-801 and ketamine, which are non-competitive blockers of N-methyl-D-aspartate (NMDA) receptors. Octapeptide CCK-8S and CCK-related decapeptide ceruletide at concentrations of 10(-9)-10(-7) M dose-dependently reduced glutamate-induced neurotoxicity. A desulfated analog CCK-8NS, which acts selectively as an antagonist of CCKB receptors, also reduced glutamate neurotoxicity. The neuroprotective effects of CCK were antagonized by L-365260, a CCKB receptor antagonist, but not by L-364718, a CCKA receptor antagonist. These results suggest that CCK protects cortical neurons against NMDA receptor-mediated glutamate neurotoxicity via CCKB receptors.
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