ZINC MODULATES GABA-B BINDING IN RAT-BRAIN

The effects of ZnCl2 on [H-3]GABA binding to GABA(A) and GABA(B) binding sites were investigate-d using receptor autoradiography. At concentrations exceeding 100 mu M, zinc non-competitively inhibited GABA(B) binding in a dose dependent fashion. GABA(A) 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 GABA(B) binding but did not prevent zinc induced inhibition of GABA(B) binding, indicating a separate site of action for these cations at the GABA(B) binding site. In some regions, zinc modulates GABA(B) binding in a biphasic manner as concentrations of 10-100 mu M zinc significantly enhanced GABA(B) 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.