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Biochem Biophys Res Commun. 2001 Jul 6;285(1):142-6.

Ni(2+), a double-acting inhibitor of neuronal nitric oxide synthase interfering with L-arginine binding and Ca(2+)/calmodulin-dependent enzyme activation.

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  • 1Zoological Station "Anton Dohrn", Villa Comunale, Naples, I-80121, Italy. palumbo@alpha.szn.it


Ni(2+), a toxic and carcinogenic pollutant and one of the leading causes of contact dermatitis, is shown to inhibit neuronal nitric oxide synthase (nNOS) in a competitive, reversible manner with respect to the substrate l-arginine (K(i) = 30 +/- 4 microM). The IC(50) values were dependent on calmodulin (CaM) concentration, but proved independent of Ca(2+), tetrahydrobiopterin (BH(4)) and other essential cofactors. Ni(2+) also inhibited CaM-dependent cytochrome c reduction, NADPH oxidation, and H(2)O(2) production by nNOS. Overall, the action profile of Ni(2+) was suggestive of an unusual, double-acting inhibitor of nNOS affecting l-arginine-binding and Ca(2+)/CaM-dependent enzyme activation.

Copyright 2001 Academic Press.

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