Release of amino acids by zinc in the hippocampus

Zinc exists in the synaptic vesicles of hippocampal mossy fibers in high concentrations. On the basis of inhibitory zinc action against glutamate release in the hippocampus, the role of zinc in release of several amino acids were studied in rat hippocampus by using in vivo microdialysis. When the hippocampal CA3 region was perfused with 10 microM ZnCl(2), the concentrations of glutamine, serine, arginine, aspartate, and glycine in the perfusate were significantly increased, whereas the concentrations of amino acids except for glycine were not increased by perfusion with 30 microM ZnCl(2). Chelation of endogenous zinc with 50 microM CaEDTA significantly decreased the concentrations of amino acids in the perfusate except for glycine. In the CA1 region, on the other hand, the concentrations of these five amino acids were not increased by perfusion with 10 microM ZnCl(2) and the concentrations of glutamine and glycine were decreased significantly. The present study suggests that zinc enhances release of glutamine, serine, arginine, and aspartate in the CA3 region and attenuates release of glutamine and glycine in the CA1 region. Zinc seems to modulate glutamatergic synapses multifunctionally in the hippocampus, because glutamine, serine, aspartate, and glycine are involved in synaptic neurotransmission.