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.
Masferrer
J L
JL
Department of Pharmacology, New York Medical College, Valhalla 10595.
Rios
A P
AP
Schwartzman
M L
ML
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D002417:Cattle; D003315:Cornea / Q000187:drug effects* / Q000201:enzymology; D004285:Dogs; D004347:Drug Interactions; D006321:Heart / Q000187:drug effects*; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D007672:Kidney Cortex / Q000187:drug effects* / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology*; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D013237:Stereoisomerism
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D016718:Arachidonic Acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase