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)
Fink
K
K
Institute of Pharmacology and Toxicology, University of Bonn, Germany.
Göthert
M
M
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005632:Fructose / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D005947:Glucose / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D012965:Sodium Chloride / Q000494:pharmacology; D013268:Stimulation, Chemical; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D058787:GABA-A Receptor Antagonists; D009943:Organophosphorus Compounds; D005632:Fructose; D012701:Serotonin; D012965:Sodium Chloride; D005680:gamma-Aminobutyric Acid; C066430:CGP 35348; D005947:Glucose; D009638:Norepinephrine; D004121:Dimethyl Sulfoxide