Zinc modulates GABAB binding in rat brain.
The effects of ZnCl2 on [3H]GABA binding to GABAA and GABAA binding sites were investigated using receptor autoradiography. At concentrations exceeding 100 microM, zinc non-competitively inhibited GABAB binding in a dose dependent fashion. GABAA binding was not inhibited significantly by zinc eliminating the possibility of a non-specific effect of zinc. Increased calcium concentrations up to 10 mM enhanced total GABAB binding but did not prevent zinc induced inhibition of GABAB binding, indicating a separate site of action for these cations at the GABAB binding site. In some regions, zinc modulates GABAB binding in a biphasic manner as concentrations of 10-100 microM zinc significantly enhanced GABAB binding in the hippocampus and the molecular layer of the cerebellum but not in the thalamus. These results provide further evidence for a neuromodulatory role for zinc in the central nervous system.
Turgeon
S M
SM
Neuroscience Program, University of Michigan, Ann Arbor.
Albin
R L
RL
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013788:Thalamus / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018756:GABA Antagonists; D005680:gamma-Aminobutyric Acid; D015032:Zinc