Intracellular localization and activation of endothelial nitric oxide synthase

Nitric oxide production by the Ca2+/calmodulin-dependent enzyme endothelial nitric oxide synthase primarily reflects changes in: intracellular [Ca2+], increasing as Ca2+ rises and decreasing as Ca2+ falls, This simplistic bim odal mechanism of regulation, has recently been refined by the finding that the binding of Ca2+/calmodulin to endothelial nitric oxide synthase involv es the disruption of the association of endothelial nitric oxide synthase f rom the scaffolding protein caveolin and the subsequent translocation of th e enzyme from plasmalemmal caveolae. Moreover, other endothelial nitric oxi de synthase-associated proteins could account for a delayed Ca2+-independen t activation of nitric oxide production, and may tie involved with caveolin in the reversible trafficking of a large endothelial nitric oxide synthase -containing heterocomplex between the caveolae and cytosolic cell structure s. Curr Opin Nephrol Hypertens 8:55-59. (C) 1999 Lippincott Williams & Wilk ins.