High D-glucose concentrations increase GABA release but inhibit release of norepinephrine and 5-hydroxytryptamine in rat cerebral cortex.

The effect of high D-glucose concentrations on the K+ (15-25 mM)-evoked release of [3H]GABA, [3H]norepinephrine ([3H]NE), [3H]5-hydroxy- tryptamine ([3H]5-HT) and [3H]acetylcholine ([3H]ACh) was investigated in rat cerebral cortical slices and synaptosomes superfused with Krebs' solution which normally contains 11.1 mM glucose. In slices, the release of [3H]GABA was enhanced by increasing D-glucose by 32-320 mM, the release of [3H]NE and [3H]5-HT was inhibited when D-glucose was increased by 60-320 mM but the release of [3H]ACh was not affected. The increase of [3H]GABA release and the inhibition of [3H]NE release were mimicked by D-fructose and NaCl at similar osmolarities, whereas dimethylsulfoxide (DMSO; a freely membrane-permeable drug) at equimolar concentrations failed to affect the release of [3H]GABA and [3H]NE. The GABAB receptor antagonist p-(3-aminopropyl)-p-diethoxymethyl- phosphinic acid (CGP 35348) abolished the inhibitory effect of an increase in D-glucose by 60 and 100 mM on [3H]NE release but only tended to diminish the inhibition caused by an increase by 320 mM. In synaptosomes, the K(+)-evoked release of 3H-GABA was enhanced by increasing D-glucose by 60-320 mM. The K(+)-evoked release of [3H]NE was only inhibited when D-glucose was increased by 320 mM, whereas it was not affected by an increase by 100 mM. In conclusion, high D-glucose differentially influences neurotransmitter release in the brain cortex. Hyperosmolarity in the extracellular fluid together with an osmotic gradient extra- versus intracellular probably plays a role in the mechanism(s) underlying the changes observed.(ABSTRACT TRUNCATED AT 250 WORDS)