Calmodulin inhibitors, W-7 and TFP, block the calmodulin-independent activation of NADPH-oxidase by arachidonate in a cell-free system.
The calmodulin inhibitor, N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7), or trifluoperazine inhibited not only Fc gamma-receptor mediated cytosolic free Ca2+ increase and O2- generation in macrophages, but also an arachidonate-induced activation of NADPH-oxidase in a cell-free system. Although these results suggested the involvement of Ca2+-calmodulin system, the cell-free activation of NADPH-oxidase occurred in the presence of EGTA and addition of calmodulin had no effect. Furthermore W-7 shifted the optimal concentration of arachidonate required for the activation to a higher level, suggesting that W-7 may block the interaction between arachidonate and NADPH-oxidase system rather than inhibiting a Ca2+-calmodulin system.
Sakata
A
A
Department of Biochemistry, Kumamoto University Medical School, Japan.
Ida
E
E
Tominaga
M
M
Onoue
K
K
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002474:Cell-Free System; D003600:Cytosol / Q000378:metabolism; D004789:Enzyme Activation; D006168:Guinea Pigs; D007700:Kinetics; D008264:Macrophages / Q000201:enzymology*; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019255:NADPH Oxidases; D013449:Sulfonamides / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D014268:Trifluoperazine / Q000494:pharmacology*
D001095:Arachidonic Acids; D002147:Calmodulin; D013449:Sulfonamides; D013481:Superoxides; D014268:Trifluoperazine; D016718:Arachidonic Acid; C017967:W 7; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D002118:Calcium