CHOLECYSTOKININ-GABA INTERACTIONS IN RODENT CORTEX - ANALYSES OF CHOLECYSTOKININ EFFECTS ON K-GLUTAMATE-INDUCED AND L-GLUTAMATE-INDUCED RELEASE OF [H-3] GABA FROM RAT CORTICAL SLICES AND CULTURED MOUSE CORTICAL-NEURONS()

Neurones of the cerebral cortex immunoreactive for the neuropeptide, c holecystokinin (CCK), also invariably contain GABA. Hence CCK is belie ved to modulate some aspect of GABAergic synaptic activity. The presen t study therefore investigated the effects of CCK on basal, K+- and L- glutamate induced release of [H-3]GABA from slices of rat neocortex an d cultured murine neocortical neurones. Rat neocortical prisms loaded with [H-3]GABA (10 nM) were superfused with Krebs-Henseleit buffer and stimulated twice (S-1 and S-2, 2 min) with K+ (30 mM). Release associ ated with each stimulus was measured and expressed relative to basal r elease (R(1) and R(2)). The effects of non-selective and CCKB selectiv e agonists, CCK-8S and CCK-4, respectively, on basal and K+-induced re lease of [H-3]GABA were subsequently assessed by alternately including the peptides in S-2 and comparing R(2)/R(1) and S-2/S-1 ratios to con trol experiments. Contrary to previous findings, CCK-8S (30 nM-1 mu M) and CCK-4 (0.3 nM-1 mu M) failed to influence basal or K+-induced rel ease. In similar experiments, murine cortical neurones superfused with HEPES balanced salt buffer, released exogenous [H-3]GABA upon stimula tion (1 min) with either K+ (55 mM) or L-glutamate (30 mu M). However, CCK-8S, CCK-4 (both 300 nM-1 mu M) and the CCKB selective antagonist, L365,260 (1 mu M), failed to influence basal, K+- or L-glutamate-indu ced release of [H-3]GABA from these neurones when included in S-2. The se data therefore do not support the postulate that CCK acting via CCK A or CCKB receptors modulates release of GABA under the present experi mental conditions. GABA-CCK interactions were not specifically studied because only L-glutamate (30 mu M) significantly elevated release of CCK-like immunoreactivity (115% above basal) in murine cortical neuron es: basal release of CCK was estimated to be 7 and 11 pM from neurones and slices, respectively. Further studies employing more rigorous sti mulation and perhaps examining endogenous GABA release are necessary t o fully investigate thee co-release of CCK and GABA. Copyright (C) 199 6 Published by Elsevier Science Ltd