Recent studies on cell cultures have indicated that the neuropeptide cholecystokinin (CCK) can prevent glutamate-induced cytotoxicity. In a preparation of rat cortical tissue placed into a two-compartment bath, the cortical tissue could be depolarized, relative to the corpus callosum, by superfusions of KCl or glutamate (1.25-10 mM). Caerulein (1-100 nM), a CCK receptor agonist, caused a rightward shift of the glutamate dose-response curve. The effect of caerulein was abolished by adding L365,260 (1 microM), a selective CCKB receptor antagonist. These findings suggest that CCK may be a physiological antagonist of glutamate-mediated neurotransmission in the rat brain.
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