title: Hypertonicity increases sodium transporters in cortical collecting duct cells independently of PGE2.
abstract: Cyclooxygenase-2 (COX-2) expression is increased by hypertonicity. Therefore we hypothesized that hypertonicity increased PGE(2) can modulate the sodium transporters (Na(+)/K(+)-ATPase: NKA, epithelial sodium channel: ENaC, and sodium hydrogen exchanger: NHE) in M1 cortical collecting duct (CCD) cells. We demonstrated by immunoblotting a 2-fold increase in NKA expression and activity following hypertonic treatment. α-ENaC was also increased, however sgk1, an ENaC activator, decreased in response to hypertonicity. Other CCD sodium transporters (β-ENaC, NHE) were unchanged. Hypertonicity also increased PGE(2) but EP(4) receptor mRNA was unaltered. PGE(2) increased intracellular Na(+) and cAMP production in M1 cells, but PGE(2)-stimulated cAMP response was attenuated by hypertonicity. Overall, PGE(2) had no effect on sodium transporter levels. Since neither COX inhibition nor EP(4) siRNA altered the induction of NKA, we propose that sodium transporter regulation by hypertonicity is independent of PGE(2). Altogether, these data indicate that despite a concomitant increase in PGE(2) production and sodium transporter expression in hypertonicity, both pathways are acting independently of each other.
authors.affiliation: Department of Cellular and Molecular Medicine, Kidney Research Centre, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada K1H 8M5.
authors.forename: Rania
authors.initials: R
authors.lastname: Nasrallah
authors.forename: Geneviève
authors.initials: G
authors.lastname: Paris
authors.forename: Richard L
authors.initials: RL
authors.lastname: Hébert
mesh_terms: D000818:Animals; D002460:Cell Line; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D034741:RNA, Small Interfering / Q000235:genetics; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000037:antagonists & inhibitors / Q000235:genetics; D012462:Saline Solution, Hypertonic / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D053503:Epithelial Sodium Channels; C545651:Ptger4 protein, mouse; D034741:RNA, Small Interfering; D058309:Receptors, Prostaglandin E, EP4 Subtype; D012462:Saline Solution, Hypertonic; D000254:Sodium-Potassium-Exchanging ATPase