Inhibition of renal, cardiac and corneal (Na(+)-K+)ATPase by 12(R)-hydroxyeicosatetraenoic acid.

12(R)-hydroxy-5,8,10,14-eicosatetraenoic acid [12(R)-HETE] is one of the major arachidonate metabolites of the corneal epithelial cytochrome P450 system. We studied its inhibitory effect on different preparations of (Na(+)-K+)ATPase. 12(R)-HETE had no effect on ATPase activity in the absence of Na+ and K+. However, it inhibited ouabain-sensitive (Na(+)-K+)ATPase obtained from bovine corneal epithelium, rat kidney and rat heart ventricle in a concentration-dependent manner with an IC50 of 10(-6) M. Its enantiomer, 12(S)-HETE, was inactive at 10(-7) M and 10(-6) M, but it inhibited (Na(+)-K+)ATPase at higher doses, an effect also seen with arachidonic acid. 12(R)-HETE as an endogenous metabolite of arachidonic acid may modulate physiological and pathophysiological processes by affecting (Na(+)-K+)ATPase activities in vivo.