Summary
Soluble guanylate cyclase in the 100,000×g supernatant fraction from bovine adrenal cortex homogenates can be activated by the NO-generating compounds sodium nitroprusside (SNP) and N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), a highly potent carcinogen. The enzyme shows also enhanced activity upon treatment with another group of activators: non-ionic detergents, phospholipase A, and unsaturated fatty acids.
Each group of stimulators yields a different form of guanylate cyclase with distinct characteristics: Exposure to NO-generating agents leads to a guanylate cyclase which possesses a high activity in the presence of either Mg2+ or Mn2+. The enzyme shows adenylate cyclase activity provided the latter cation is present. However, no adenylate cyclase activity is observed with the soluble enzyme preparation exposed to the second group of activators, and Mn2+ remains the preferred cation under these conditions.
Pretreatment with nonionic detergents, phospholipase A or unsaturated fatty acids on the other hand, inhibits activation of the soluble enzyme preparation by SNP or MNNG. This inhibition is partial for guanylate cyclase activity and complete for adenylate cyclase activity. It can not be overcome by further administration of the NO-generating activators.
The results presented in this communication support the following hypothesis: The soluble guanylate cyclase from bovine adrenal cortex contains hydrophobic sites where ligands like nonionic detergents or unsaturated fatty acids are bound and oxidizable sites necessary for the action of SNP and MNNG. These sites regulate enzyme activity as well as substrate and cation specificity.
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with technical assistance of Cornelika Konrad and Ludwig Braun
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Struck, CJ., Glossmann, H. Soluble bovine adrenal cortex guanylate cyclase: Effect of sodium nitroprusside, nitrosamines, and hydrophobic ligands on activity, substrate specificity and cation requirement. Naunyn-Schmiedeberg's Arch. Pharmacol. 304, 51–61 (1978). https://doi.org/10.1007/BF00501377
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DOI: https://doi.org/10.1007/BF00501377