RT Journal Article
SR Electronic
T1 The Activation of Neuronal Nitric-Oxide Synthase by Various Divalent Cations
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 781
OP 786
DO 10.1124/jpet.102.035337
VO 302
IS 2
A1 John Weaver
A1 Supatra Porasuphatana
A1 Pei Tsai
A1 Guan-Liang Cao
A1 Theodore A. Budzichowski
A1 Linda J. Roman
A1 Gerald M. Rosen
YR 2002
UL http://jpet.aspetjournals.org/content/302/2/781.abstract
AB Nitric-oxide synthase (NOS; EC 1.14.13.39) catalyzes the oxidation ofl-arginine to nitric oxide (NO⋅) andl-citrulline via the intermediateNω-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. The American Society for Pharmacology and Experimental Therapeutics