Involvement of Hg2+-sensitive sulfhydryl groups in regulating noradrenaline release induced by S-nitrosocysteine in rat brain slices

Nitric oxide has been shown to regulate neurotransmitter release. Previously, we reported that S-nitrosothiols such as S-nitrosocysteine (SNC) stimulate noradrenaline (NA) release in rat hippocampus in vivo and in vitro. To examine the role of sulfhydryl groups in SNC-induced NA release, the effects of metal ions such as Hg2+ and N-ethylmaleimide (NEM, a sulfhydryl alkylating agent) on [H-3]NA release from labeled rat brain slices (hippocampus and cerebral cortex) were studied and compared with the effects of SNC. The addition of 200 mu M HgCl2, but not Pb2+, Zn2+, or Cd2+, stimulated [H-3]NA release from both types of slices in the presence of extracellular CaCl2. p-Chloromercuribenzoic acid (p-CMBA) also stimulated [H-3]NA release. NEM stimulated [H-3]NA release from both types of slices in the-presence and absence of extracellular CaCl2. The effect of 200 mu M NEM was enhanced, but the effect of 200 mu M SNC was inhibited by co-addition of 200 mu M p-CMBA in the absence of extracellular CaCl2. The concentration-response curve of SNC shifted to the right ;after co-addition of 200 mu M p-CMBA or 100 mu M HgCl2, although the effect of 200 mu M NEM was additive to the effect of SNC. These findings demonstrate that SNC acts as a sulfhydryl agent on proteins that regulate NA release, and that SNC may share the same sulfhydryl groups with:Hg compounds. The effect of T-588 {(R)-(-)-(benzo[b]thiophen-5-yl)-2-[2-(N,N-diethylamino)ethoxy]ethanol hydrochloride}, a novel cognitive enhancer and a stimulator of NA release, was compared with the effects of sulfhydryl reagents. BIOCHEM PHARMACOL 59;7:839-845, 2000. (C) 2000 Elsevier Science Inc.