Sulfhydryl reagents trigger noradrenaline release from rat brain slices

• Published in: Japanese Journal of Pharmacology Vol. 76; no. suppl.2; p. 254
• Main Authors: Mutsuko Maekawa, Souichi Satoh, Toshihiko Murayama, Yasuyuki Nomura
• Format: Journal Article
• Language: Japanese
• Published: The Japanese Pharmacological Society 1998
• ISSN: 0021-5198; 1347-3506

Heavy metals like Hg^2+ , Ag^+ , Cu^2+ and Zn^2+ were shown to induce Ca^2+ release from sarcoplasmic reticulum (SR) vesicles by binding to an accessible free sulfhydryl (SH) on a protein. However, the effects of metals on neuronal cells have not been well established. We found that HgCl_2 (200 μM), not other metal cations, stimulated [^^3 H]NA release from rat brain slices. This stimulatory effect was Ca^2+ -dependent p-Chloromercuri benzoic acid (p-CMBA), which is known to make mercaptide on protein, also stimulated [^^3 H]NA release in cerebral cortical slices. The SH-alkylating agent N-ethylmaleimide (NEM) and S-nitroso-L-cysteine (SNC), which is known to make S-nitrosothiol on protein, stimulated [^^3 H]NA release in both the presence and absence of extracellular CaCl_2 . Additionally, pretreatment with 5 mM dithiothreitol (DTT), a SH-reducing agent, completely inhibited HgCl_2 , p-CMBA and NEM-stimulated [^^3 H]NA release. The dose-response curve for SNC was shifted upwardby 200 μM NEM, and was shifted rightward by 100 μM HgCl_2 and 200 μM p-CMBA. The addition of 200 μM p-CMBA to the assay buffer enhanced the effects of 200 μM NEM from 12.4±1.1% to 23.2±2.1%, while p-CMBA reduced the effects of 200 μM SNC from 24.5±1.7% to 12.4±1.2%. These findings suggest that 1) Hg^2+ NEM and SNC stimulate NA release via SH group modification, 2) there may be a multiple SH groups-mediated process in NA release. Previously, we reported that T-588 (a novel cognitive enhancer) stimulated [^^3 H]NA release. T-588 was not affected by DT[^^3 H] and p-CMBA. The mechanism of the effects of T-588 seems to be different from that of SH reagents.