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 [3H]NA release from labeled rat brain slices (hippocampus and cerebral cortex) were studied and compared with the effects of SNC. The addition of 200 microM HgCl2, but not Pb2+, Zn2+, or Cd2+, stimulated [3H]NA release from both types of slices in the presence of extracellular CaCl2. p-Chloromercuribenzoic acid (p-CMBA) also stimulated [3H]NA release. NEM stimulated [3H]NA release from both types of slices in the presence and absence of extracellular CaCl2. The effect of 200 microM NEM was enhanced, but the effect of 200 microM SNC was inhibited by co-addition of 200 microM p-CMBA in the absence of extracellular CaCl2. The concentration-response curve of SNC shifted to the right after co-addition of 200 microM p-CMBA or 100 microM HgCl2, although the effect of 200 microM 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]eth anol hydrochloride¿, a novel cognitive enhancer and a stimulator of NA release, was compared with the effects of sulfhydryl reagents.
Maekawa
M
M
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Satoh
S
S
Murayama
T
T
Nomura
Y
Y
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002122:Calcium Chloride / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004048:Diethylamines / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008627:Mercuric Chloride / Q000494:pharmacology; D008628:Mercury / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D026403:S-Nitrosothiols; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology; D020245:p-Chloromercuribenzoic Acid / Q000494:pharmacology
D000697:Central Nervous System Stimulants; D004048:Diethylamines; D009603:Nitroso Compounds; D026403:S-Nitrosothiols; D013438:Sulfhydryl Compounds; D013876:Thiophenes; C082372:T 588; D008627:Mercuric Chloride; D020245:p-Chloromercuribenzoic Acid; C021315:S-nitrosocysteine; D008628:Mercury; D003545:Cysteine; D002122:Calcium Chloride; D005033:Ethylmaleimide; D009638:Norepinephrine