Isoform-specific effects of salts on nitric oxide synthase activity

We investigated the effects of salts on the properties of the neuronal, endothelial, and inducible isoforms of nitric oxide synthase (nNOS, eNOS, and iNOS), and found pronounced isoform-specific effects on NOS-catalyzed L-citrulline formation. Salts inhibited iNOS monotonously, whereas nNOS and eNOS were stimulated up to 3-fold at low, and inhibited at high (>/=0.1-0.2 M) salt concentrations. The effectivities of different ions mostly followed the Hofmeister series, indicating that the effects can for a large part be ascribed to changes in protein solvation. Km(Arg) increased in the presence of NaCl, demonstrating the importance of charge interactions for substrate binding. The coupling of NADPH oxidation to NO production was not affected by KCl. Salts (