Calcium‐dependent nitric oxide synthesis in endothelial cytosol is mediated by calmodulin

FEBS Letters

Mülsch, Alexander¹  Busse, Rudi¹ 

[1] Department of Applied Physiology, University of Freiburg, Hermann-Herder-Str. 7, D-7800 Freiburg, FRG

关键词: Nitric oxide;    Soluble guanylate cyclase;    Endothelial cytosol;    Calmodulin;    Nitric oxide synthase;   

DOI  :  10.1016/0014-5793(90)80902-U

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We investigated whether calmodulin mediates the stimulating effect of Ca²⁺ on nitric oxide synthase in the cytosol of porcine aortic endothelial cells. Nitric oxide was quantified by activation of a purified soluble guanylate cyclase. The Ca²⁺-sensitivity of nitric oxide synthase was lost after anion exchange chromatography of the endothelial cytosol and could only be reconstituted by addition of calmodulin or heat-denatured endothelial cytosol. The Ca²⁺-dependent activation of nitric oxide synthase in the cytosol was inhibited by the calmodulin-binding peptides/proteins melittin, mastoparan, and calcineurin (IC₅₀ 450, 350 and 60 nM, respectively), but not by the calmodulin antagonist, calmidazolium. In contrast, Ca²⁺-calmodulin-reconstituted nitric oxide synthase was inhibited with similar potency by melittin and calmidazolium. The results suggest that the Ca²⁺-dependent activation of nitric oxide synthase in endothelial cells is mediated by calmodulin.

【 授权许可】

Unknown