Under anaerobic conditions, soluble guanylate cyclase is specifically stimulated by glutathione.
Various thiols exert non-specific effects on the activity of soluble guanylate cyclase under aerobic conditions. We studied the effects of thiols under anaerobic conditions (pO2 less than 6 Torr) on soluble guanylate cyclase, purified from bovine lung. Reduced glutathione stimulated the enzyme concentration-dependently with half-maximal enzyme stimulation at a concentration of about 0.5 mM. The extend of maximal enzyme stimulation (up to 80-fold) was comparable with the activation by NO-containing substances. The activation by glutathione was additive with the effect of sodium nitroprusside. Cysteine and various other thiols increased the enzyme activity 20-fold and 2- to 5-fold, respectively. The stimulatory effect of these thiols was not related to their reducing potency. Activation of soluble guanylate cyclase by glutathione was dose-dependently reduced in the presence of other thiols (cysteine greater than oxidized glutathione greater than S-methyl glutathione). Under aerobic conditions or with Mn-GTP as substrate, the effect of glutathione on soluble guanylate cyclase was suppressed. The results suggest a specific role for glutathione in the regulation of soluble guanylate cyclase activity and a modulation of this effect by redox reactions and other intracellular thiols.
Niroomand
F
F
Pharmakologisches Institut, Universität Heidelberg, F.R.G.
Rössle
R
R
Mülsch
A
A
Böhme
E
E
D000693:Anaerobiosis; D000818:Animals; D002417:Cattle; D004789:Enzyme Activation / Q000187:drug effects; D005978:Glutathione / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008168:Lung; D010084:Oxidation-Reduction; D012995:Solubility; D013438:Sulfhydryl Compounds / Q000494:pharmacology
D013438:Sulfhydryl Compounds; D006162:Guanylate Cyclase; D005978:Glutathione