Ibuprofen-induced changes in sulfate renal transport.
Nonsteroidal anti-inflammatory drugs (NSAIDs) increase sulfate renal clearance and decrease the fractional reabsorption of sulfate by the kidneys. The mechanism of this alteration of inorganic sulfate homeostasis is unknown. The objectives of this study were 1) to investigate if sulfate renal transport is altered in isolated membrane vesicles after pretreatment of animals in vivo with ibuprofen (IBU), and 2) to determine the cellular mechanism of changes in sulfate renal transport. Female Lewis rats received IBU at a i.v. dose of 27 mg/kg followed by an infusion of 33 microg/min for 4 hr. Sulfate transport was studied using brush border (BBM) and basolateral membrane (BLM) vesicles isolated from rat kidney cortex. The Vmax for the sodium-dependent sulfate cotransport (NaSi-1) in BBM was significantly lower in the IBU group compared with the control group (0.79 +/- 0.23 vs. 1.25 +/- 0.17 nmol/mg protein/10 sec, respectively; P <.05) with no change in Km. There were no significant differences between the study groups in sulfate anion exchange kinetics in BLM vesicles. NaSi-1 transporter mRNA level in kidney cortex and protein level in BBM were significantly lower in animals pretreated with IBU compared with that in control animals. There was no change in membrane fluidity of BBM and BLM isolated from IBU-treated animals as measured by the fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene. These results indicate that IBU treatment alters sodium-dependent sulfate cotransport by a downregulation of mRNA and protein of NaSi-1 transporter in BBM.
Sagawa
K
K
Department of Pharmaceutics, State University of New York at Buffalo, Amherst, New York, USA.
Benincosa
L J
LJ
Murer
H
H
Morris
M E
ME
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001692:Biological Transport; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D027682:Cation Transport Proteins; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007052:Ibuprofen / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008560:Membrane Fluidity / Q000187:drug effects; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D000077003:Sodium Sulfate Cotransporter; D013431:Sulfates / Q000378:metabolism*; D027981:Symporters
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D012333:RNA, Messenger; D000077003:Sodium Sulfate Cotransporter; D013431:Sulfates; D027981:Symporters; D007052:Ibuprofen