Cholecystokinin-8 increases K +-evoked [ 3H]γ-aminobutyric acid release in slices from various brain areas

Abstract

[ 3H]γ-Aminobutyric acid (GABA) release was studied in rat brain slices in the absebce or presence of cholecystokinin-8 (CCK-8). [ 3H]GABA release under the conditions used was Ca 2+-dependent and insensitive tot he presence of the glial uptake blocker β-alanine. While the basal release of [ 3H]GABA was not affected by CCK-8, the K +-stimulated release of [ 3H]GABA wasm significantly enhanced by 300 nM of CCK-8 in the caudate putamen, the substantia nigra, the hippocampal formation and the parietofrontal cortex. In the cerebral cortex the CCK-8 enhancement of [ 3H]GABA release was concentration-dependent and abolished by the CCK B receptor antagonists PD135,158 (1.0 nM) and L-365,260 (100 nM). A significant counteraction of the CCK-8 action was also found with the CCK A receptor antagonist L-364,718 (100 nM) but only in concentrations at which both CCK A and CCK B receptors are blocked. No CCK-8 effects on [ 3H]GABA release were observed when tetrodotoxin was superfused 5 min before the K +-induced [ 3H]GABA release. It is suggested that the enhancing actions of CCK-8 on K +-stimulated [ 3H]GABA release is mainly related to an activation of CCK B receptors.