Tumor necrosis factor alpha down-regulates the Na+-K+ ATPase and the Na+-K+2Cl- cotransporter in the kidney cortex and medulla.
The effect of TNF-alpha on the renal Na+-K+ pump and the Na+-K+2Cl- cotransporter was investigated in the rat. Animals were injected with the cytokine, and 4h later, a homogenate from the cortical and medullary tissues was prepared and used to assay the activity of the Na+-K+ ATPase and the protein expression of the pump and symporter. TNF-alpha reduced the activity and expression of the pump in both cortex and medulla, and its effect disappeared when animals were pre-treated with indomethacin, suggesting that TNF-alpha acts via PGE2. Higher levels of PGE2 were detected by enzyme immunoassay, in kidney tissues isolated from rats treated with PGE2, thus confirming this hypothesis. The cytokine also down-regulated the Na+-K+2Cl- cotransporter but this effect was not abrogated by indomethacin. PGE2, injected into animals, exerted a dose-dependent effect. Low doses did not have any effect on the two transporters in the cortex while high doses inhibited and down-regulated the pump and up-regulated the cotransporter. In the medulla low doses increased the activity and expression of the pump but down-regulated the cotransporter while high doses exerted an exactly opposite effect on the two transporters. It was concluded that the effect of TNF-alpha on the pump is mediated via PGE2 which is released at relatively high doses. The effect of the cytokine on the cotransporter is, however, independent of PGE2.
Department of Biology, Faculty of Arts and Sciences, American University of Beirut, Beirut, Lebanon. sawkreyd@aub.edu.lb
Sawsan Ibrahim
SI
Kreydiyyeh
Sarine
S
Markossian
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D007213:Indomethacin / Q000494:pharmacology; D007672:Kidney Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D007679:Kidney Medulla / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D028021:Sodium-Potassium-Chloride Symporters; D014409:Tumor Necrosis Factor-alpha; D000254:Sodium-Potassium-Exchanging ATPase; D015232:Dinoprostone; D007213:Indomethacin