Epithelial Nitric Oxide Synthase eNOS

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Epithelial Nitric Oxide Synthase (eNOS)
SIGMA-ALDRICH
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Epithelial Nitric Oxide Synthase (eNOS) Nitric
Oxide (NO) produced in the endothelial cells is
involved in vasorelaxation, platelet aggregation,
and mechanisms of cardiovascular homeostasis.
Endothelial nitric oxide synthase (eNOS, cNOS,
Type III) is constitutively expressed in
endothelial and other cell types. Myristoylation
and palmitoylation maintain the localization of
eNOS to caveolae in the plasma membrane of
resting cells where it is bound to caveolin. eNOS
is inactive in the membrane-bound state.
Activation of endothelial acetylcholine receptors
activate phospholipase C (PLC) that catalyzes the
production of inositol 1,4,5-trisphosphate (IP3)
and diacylglycerol (DAG) from phosphatidylinositol
4,5-bisphosphate (PIP2). The IP3-induced
increase in intracellular Ca2 activates
calmodulin that binds to eNOS, which dissociates
from caveolin and translocates to the cytoplasm.
Phosphorylation of eNOS by protein kinase A (PKA)
inactivates the enzyme, which then relocates to
the membrane caveoli. References Ghosh, S., et
al., Interaction between caveolin-1 and the
reductase domain of endothelial nitric-oxide
synthase. Consequences for catalysis. J. Biol.
Chem., 273, 22267-22271 (1998). Arnal, J.F., et
al., Endothelium-derived nitric oxide and
vascular physiology and pathology. Cell. Mol.
Life Sci., 55, 1078-1087 (1999). Yeh, D.C., et
al., Depalmitoylation of endothelial nitric-oxide
synthase by acylprotein thioesterase 1 is
potentiated by Ca2-calmodulin. J. Biol. Chem.,
274, 33148-33154 (1999).