Regulation of renal epithelial cell affinity for calcium oxalate monohydrate crystals.
The binding and internalization of calcium oxalate monohydrate (COM) crystals by tubular epithelial cells may be a critical step leading to kidney stone formation. Exposure of MDCK cells to arachidonic acid (AA) for 3 days, but not oleic or linoleic acid, decreased COM crystal adhesion by 55%. Exogenous prostaglandin PGE(1) or PGE(2) decreased crystal binding 96% within 8 h, as did other agents that raise intracellular cAMP. Actinomycin D, cycloheximide, or tunicamycin each blocked the action of PGE(2), suggesting that gene transcription, protein synthesis, and N-glycosylation were required. Blockade of crystal binding by AA was not prevented by the cyclooxygenase inhibitor flurbiprofen, and was mimicked by the nonmetabolizable AA analog eicosatetryanoic acid (ETYA), suggesting that generation of PGE from AA is not the pathway by which AA exerts its effect. These studies provide new evidence that binding of COM crystals to renal cells is regulated by physiological signals that could modify exposure of cell surface molecules to which the crystals bind. Intrarenal AA, PGs, and/or other agents that raise the intracellular concentration of cAMP may serve a protective function by preventing crystal adhesion along the nephron, thereby defending the kidney against crystal retention and stone formation.
Lieske
J C
JC
Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA. jlieske@medicine.bsd.uchicago.edu
Huang
E
E
Toback
F G
FG
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D002129:Calcium Oxalate / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D003460:Crystallization; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004285:Dogs; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D007669:Kidney Calculi / Q000517:prevention & control; D007684:Kidney Tubules / Q000378:metabolism*
D015117:5,8,11,14-Eicosatetraynoic Acid; D002129:Calcium Oxalate; D016718:Arachidonic Acid; D000242:Cyclic AMP; D000527:Alprostadil; D015232:Dinoprostone