Zinc inhibition of GABA-stimulated Cl- influx in rat brain regions is unaffected by acute or chronic benzodiazepine.
Zinc modulation of GABAA receptor function was studied using GABA-stimulated 36Cl- influx into microsacs prepared from rat cerebral cortex, cerebellum and hippocampus. Zinc (10-100 microM) did not affect the basal influx, but significantly inhibited GABA-stimulated 36Cl- influx. The inhibition appeared to be noncompetitive. Zinc produced differing degrees of inhibition of GABA-stimulated 36Cl- influx in different brain regions. The order of sensitivity to zinc inhibition of GABA-stimulated 36Cl- influx was hippocampus > cerebral cortex > cerebellum. These regional differences may reflect the structural heterogeneity of GABAA receptors among brain areas. Zinc inhibition was not affected by the short-term addition of three benzodiazepines, diazepam, bretazenil and triazolam. The effect of diazepam and bretazenil to potentiate GABA-stimulated 36Cl- influx was not affected by zinc, but the effect of triazolam was decreased by zinc. In brain tissue prepared from flurazepam-treated rats, there was no difference compared with controls in zinc inhibition of GABA-stimulated 36Cl- influx. The results indicate that the effects of zinc on the GABAA receptor are largely independent of drugs acting on the benzodiazepine binding site.
Li
M
M
Department of Pharmacology, Medical College of Ohio, Toledo 43699-0008.
Rosenberg
H C
HC
Chiu
T H
TH
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects*; D002712:Chlorides / Q000378:metabolism*; D002713:Chlorine; D005479:Flurazepam / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D011868:Radioisotopes; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects; D015032:Zinc / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D002712:Chlorides; D018756:GABA Antagonists; D011868:Radioisotopes; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D002713:Chlorine; D005680:gamma-Aminobutyric Acid; D005479:Flurazepam; D015032:Zinc