INVOLVEMENT OF L-TYPE-LIKE AMINO-ACID TRANSPORTERS IN S-NITROSOCYSTEINE-STIMULATED NORADRENALINE RELEASE IN THE RAT HIPPOCAMPUS

Nitrogen oxides, such as nitric oxide, have been shown to regulate neu ronal functions, including neurotransmitter release. We investigated t he effect of S-nitroso-L-cysteine (SNC) on noradrenaline (NA) release in the rat hippocampus in vivo and in vitro. SNC stimulated [H-3]NA re lease from prelabeled hippocampal slices in a dose-dependent manner. S NC stimulated endogenous NA release within 30 min to almost five times the basal level in vivo (microdialysis in freely moving rats). In a N a+-containing Tyrode's buffer, SNC-stimulated [H-3]NA release was inhi bited 30% by the coaddition of L-leucine. In the Na+-free, choline-con taining buffer, SNC-stimulated [H-3]NA release, which was similar to t hat in the Na+-containing buffer, was inhibited markedly by L-leucine, L-alanine, L-methionine, L-phenylalanine, and L-tyrosine. The effects of the other amino acids examined were smaller or very limited. The e ffect of L-leucine was stronger than that of D-leucine. A specific inh ibitor of the L-type amino acid transporter, 2-aminobicyclo [2.2.1]-he ptane-2-carboxylate (BCH), inhibited the effects of SNC on [H-3]NA rel ease in the Na+-free buffer. Uptake of L-[H-3] leucine into the slices in the Na+-free buffer was inhibited by SNC, BCH, and L-phenylalanine , but not by L-lysine. The effect of SNC on cyclic GMP accumulation wa s not inhibited by L-leucine, although SNC stimulated cyclic GMP accum ulation at concentrations up to 25 mu M, much less than the concentrat ion that stimulates NA release, These findings suggest that SNC is inc orporated into rat hippocampus via the L-type-like amino acid transpor ter, at least in Na+-free conditions, and that SNC stimulates NA relea se in vivo and in vitro in a cyclic GMP-independent manner.