19(S)-hydroxyeicosatetraenoic acid is a potent stimulator of renal Na+-K+-ATPase.
Omega- and omega-1 hydroxylations are the major pathways by which arachidonic acid is metabolized in cortical and outer medullary microsomes of rat and rabbit kidneys. It is a cytochrome P450-dependent oxidation leading to the formation of 20-hydroxy- and 19-hydroxyeicosatetraenoic acids. In this study, we compared the effects of the synthetically prepared omega- and omega-1 metabolites of arachidonic acid on the activity of the renal Na+-K+-ATPase partially purified from rat renal cortical microsomes. 19(S)-hydroxyeicosatetraenoic acid caused a dose related stimulation of Na+-K+-ATPase activity with an EC50 of 3 x 10(-7) M. In contrast, neither 19(R)-hydroxyeicosatetraenoic acid, 20-hydroxyeicosatetraenoic acid nor arachidonic acid at 10(-6) M had any effect on Na+-K+-ATPase activity. In the same preparation, ouabain at 10(-3) M and 12(R)-hydroxyeicosatetraenoic acid at 10(-6) M inhibited the enzyme activity by 75% and 60%, respectively. We conclude that 19(S)-hydroxyeicosatetraenoic acid is a specific stimulator of renal Na+-K+-ATPase. Therefore, the formation of 19(S)-hydroxyeicosatetraenoic acid by renal cortical cytochrome P450 omega-1-hydroxylase may contribute to the regulation of renal function by regulating Na+-K+-ATPase which is essential for transtubular transport processes.
Escalante
B
B
Department of Pharmacology, New York Medical College, Valhalla 10595.
Falck
J R
JR
Yadagiri
P
P
Sun
L M
LM
Laniado-Schwartzman
M
M
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology; D007672:Kidney Cortex / Q000187:drug effects / Q000201:enzymology*; D008861:Microsomes / Q000201:enzymology; D010042:Ouabain / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D006893:Hydroxyeicosatetraenoic Acids; D010042:Ouabain; C055986:19-hydroxy-5,8,11,14-eicosatetraenoic acid; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D000254:Sodium-Potassium-Exchanging ATPase