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.