title: Interleukin-1 inhibition of Na(+)-K(+)-ATPase in inner medullary collecting duct cells: role of PGE2.
abstract: Interleukin-1 (IL-1), a cytokine produced by macrophages, causes an increase in Na+ excretion in experimental animals. Micropuncture studies have determined that the natriuretic effect of IL-1 is largely due to inhibition of Na+ reabsorption in the collecting duct. The current studies made use of suspensions of rabbit inner medullary collecting duct (IMCD) cells to examine the mechanism by which IL-1 regulates Na+ transport. IL-1 reduced ouabain-sensitive 86Rb+ uptake by 48% at 10 s, 36% at 30 s, and 29% at 60 s, suggesting an inhibitory effect on Na(+)-K(+)-adenosinetriphosphatase (ATPase) activity. IL-1 inhibition of 86Rb+ uptake occurred in a dose-dependent manner. This effect appears to be mediated by prostaglandin E2 (PGE2) because 1) ibuprofen blocks the inhibitory effect of IL-1 on IMCD Na(+)-K(+)-ATPase activity, 2) IL-1 and PGE2 cause equivalent and nonadditive inhibition of 86Rb+ uptake, 3) IL-1 causes a two- to threefold increase in PGE2 content in IMCD cells, and 4) dose-response curves were similar for IL-1 stimulation of PGE2 content and inhibition of 86Rb+ uptake in IMCD cells. Thus the natriuretic effect of IL-1 is due, at least in part, to stimulation of PGE2 production by collecting duct cells with resultant inhibition of Na(+)-K(+)-ATPase activity.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: M L
authors.initials: ML
authors.lastname: Zeidel
authors.forename: H R
authors.initials: HR
authors.lastname: Brady
authors.forename: D E
authors.initials: DE
authors.lastname: Kohan
mesh_terms: D000818:Animals; D015232:Dinoprostone / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D007052:Ibuprofen / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D007685:Kidney Tubules, Collecting / Q000201:enzymology*; D011817:Rabbits; D012414:Rubidium Radioisotopes / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
chemical_list: D007375:Interleukin-1; D012414:Rubidium Radioisotopes; D000254:Sodium-Potassium-Exchanging ATPase; D015232:Dinoprostone; D007052:Ibuprofen