Regulation of CCK release in cerebral cortex by N-methyl-D-aspartate receptors: Sensitivity to APV, MK-801, kynurenate, magnesium and zinc lons

Abstract

Cholecystokinin octapeptide (CCK) is an abundant neuropeptide of cerebral cortex but its function in this region is largely unknown. In this study we have examined the effect of glutamate receptor activation on the depolarisation-induced release of CCK-like immunoreactivity from tissue slices of rat cerebral cortex. The K +-evoked release of cholecystokinin was found to be significantly increased by the three excitatory amino acid agonists effective against glutamate receptor subtypes, N-methyl-D-aspartate (NMDA), kainic acid and quisqualate. The facilitation of CCK release by NMDA was examined in more detail and shown to be significantly attenuated by Mg 2+ (2.5 mM), Zn 2+ (50 μM), MK-801 (0.1 and 0.3 μM), aminophosphonovaleric acid (100 μM) and kynurenic acid (100 μM and 300 μM). These results support the conclusion that release of CCK in cerebral cortex is modulated by the NMDA receptor.