TY - JOUR
T1 - 19(S)-hydroxyeicosatetraenoic acid is a potent stimulator of renal Na+-K+-ATPase
AU - Escalante, Bruno
AU - Falck, J R
AU - Yadagiri, Pendri
AU - Sun, Lumin
AU - Laniado-Schwartzman, Michal
N1 - Funding Information:
The authors wish to thank Amelia R. Escalante for her excellent technical assistance and Pamela Blank for typing the manuscript. This study was supported in part by the National Institutes of Health Grants HL 34300 and GM31278. M.L. Schwartzman is a recipient of the Irma T. Hirschl Career Scientist Award.
PY - 1988/5/16
Y1 - 1988/5/16
N2 - ω- and ω-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-hydroxy-eicosatetraenoic acids. In this study, we compared the effects of the synthetically prepared ω- and ω-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 3×10-7M. In contrast, neither 19(R)-hydroxyeicosatetraenoic acid, 20-hydroxyeicosatetraenoic acid nor arachidonic acid at 10-6M had any effect on Na+-K+-ATPase activity. In the same preparation, ouabain at 10-3M and 12(R)-hydroxyeicosatetraenoic acid at 10-6M 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 ω-1-hydroxylase may contribute to the regulation of renal function by regulating Na+-K+-ATPase which is essential for transtubular transport processes.
AB - ω- and ω-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-hydroxy-eicosatetraenoic acids. In this study, we compared the effects of the synthetically prepared ω- and ω-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 3×10-7M. In contrast, neither 19(R)-hydroxyeicosatetraenoic acid, 20-hydroxyeicosatetraenoic acid nor arachidonic acid at 10-6M had any effect on Na+-K+-ATPase activity. In the same preparation, ouabain at 10-3M and 12(R)-hydroxyeicosatetraenoic acid at 10-6M 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 ω-1-hydroxylase may contribute to the regulation of renal function by regulating Na+-K+-ATPase which is essential for transtubular transport processes.
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U2 - 10.1016/S0006-291X(88)80422-4
DO - 10.1016/S0006-291X(88)80422-4
M3 - Article
C2 - 2837181
AN - SCOPUS:0024289847
SN - 0006-291X
VL - 152
SP - 1269
EP - 1274
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -