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10.1152/ajprenal.00018.2020

http://scihub22266oqcxt.onion/10.1152/ajprenal.00018.2020
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suck abstract from ncbi


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pmid32308018      Am+J+Physiol+Renal+Physiol 2020 ; 318 (6): F1369-F1376
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  • Epoxyeicosatrienoic acid metabolites inhibit Kir4 1/Kir5 1 in the distal convoluted tubule #MMPMID32308018
  • Wang MX; Wang LJ; Xiao Y; Zhang DD; Duan XP; Wang WH
  • Am J Physiol Renal Physiol 2020[Jun]; 318 (6): F1369-F1376 PMID32308018show ga
  • Cytochrome P-450 (Cyp) epoxygenase-dependent metabolites of arachidonic acid (AA) have been shown to inhibit renal Na(+) transport, and inhibition of Cyp-epoxygenase is associated with salt-sensitive hypertension. We used the patch-clamp technique to examine whether Cyp-epoxygenase-dependent AA metabolites inhibited the basolateral 40-pS K(+) channel (Kir4.1/Kir5.1) in the distal convoluted tubule (DCT). Application of AA inhibited the basolateral 40-pS K(+) channel in the DCT. The inhibitory effect of AA on the 40-pS K(+) channel was specific because neither linoleic nor oleic acid was able to mimic the effect of AA on the K(+) channel. Inhibition of Cyp-monooxygenase with N-methylsulfonyl-12,12-dibromododec-11-enamide or inhibition of cyclooxygenase with indomethacin failed to abolish the inhibitory effect of AA on the 40-pS K(+) channel. However, the inhibition of Cyp-epoxygenase with N-methylsulfonyl-6-(propargyloxyphenyl)hexanamide abolished the effect of AA on the 40-pS K(+) channel in the DCT. Moreover, addition of either 11,12-epoxyeicosatrienoic acid (EET) or 14,15-EET also inhibited the 40-pS K(+) channel in the DCT. Whole cell recording demonstrated that application of AA decreased, whereas N-methylsulfonyl-6-(propargyloxyphenyl)hexanamide treatment increased, Ba(2+)-sensitive K(+) currents in the DCT. Finally, application of 14,15-EET but not AA was able to inhibit the basolateral 40-pS K(+) channel in the DCT of Cyp2c44(-/-) mice. We conclude that Cyp-epoxygenase-dependent AA metabolites inhibit the basolateral Kir4.1/Kir5.1 in the DCT and that Cyp2c44-epoxygenase plays a role in the regulation of the basolateral K(+) channel in the mouse DCT.
  • |8,11,14-Eicosatrienoic Acid/*analogs & derivatives/metabolism/pharmacology[MESH]
  • |Amides/pharmacology[MESH]
  • |Animals[MESH]
  • |Arachidonic Acid/metabolism/*pharmacology[MESH]
  • |Cytochrome P450 Family 2/antagonists & inhibitors/genetics/*metabolism[MESH]
  • |Enzyme Inhibitors/pharmacology[MESH]
  • |Kidney Tubules, Distal/*drug effects/metabolism[MESH]
  • |Male[MESH]
  • |Membrane Potentials[MESH]
  • |Mice, 129 Strain[MESH]
  • |Mice, Knockout[MESH]
  • |Potassium Channel Blockers/metabolism/*pharmacology[MESH]


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