The activation of neuronal nitric-oxide synthase by various divalent cations

John Weaver, Supatra Porasuphatana, Pei Tsai, Guan Liang Cao, Theodore A. Budzichowski, Linda J. Roman, Gerald M. Rosen

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Nitric-oxide synthase (NOS; EC 1.14.13.39) catalyzes the oxidation of L-arginine to nitric oxide (NO.) and L-citrulline via the intermediate Nω-hydroxy-L-arginine. Of the three distinct isoforms of NOS that have been characterized, the constitutive neuronal NOS (NOS I) generates NO. associated with long-term potentiation (LTP) and early brain development. All of the NOS isoforms contain an N-terminal oxidase and a C-terminal reductase domain connected by a Ca2+/calmodulin binding region. To activate NOS I, Ca2+ has to bind to calmodulin, allowing electron transport through both domains. Calcium ions are tightly regulated in cells. However, a number of other metal ions that bind and activate calmodulin may also activate NOS I. One such metal ion may be Pb2+, which is associated with neurobehavioral and psychological alterations, including the inhibition of LTP. The effect of various divalent cations on NOS I activity was tested, and the results presented herein demonstrate that Pb2+ and Sr2+ can activate NOS I to a level similar to that found for Ca2+. Finally, there is a synergy between Pb2+ and Ca2+ resulting in maximal activation of NOS I using minimal concentrations of both metal ions.

Original languageEnglish (US)
Pages (from-to)781-786
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume302
Issue number2
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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