Glucocorticoids regulate NHE-3 transcription in OKP cells.
OKP cells express NHE-3, an amiloride-resistant Na+/H+ antiporter, which is likely an isoform responsible for apical proton secretion by the proximal tubule. We have previously shown that an amiloride-resistant Na+/H+ antiporter in OKP cells is regulated by dexamethasone, a synthetic glucocorticoid. The purpose of the present study was to examine the mechanism for the glucocorticoid-mediated increase in Na+/H+ antiporter activity. Incubation of OKP cells with 10(-6) M dexamethasone resulted in a two- to threefold increase in NHE-3 mRNA abundance. This increase was seen after 4 h of incubation with dexamethasone, a time course similar to that found for Na+/H+ antiporter activity. To examine the mechanism for the increase in NHE-3 mRNA abundance, mRNA half-life and in vitro transcription experiments were performed. NHE-3 mRNA had a half-life of 8 h in control and dexamethasone-treated cells. The rate of in vitro transcription was 1.8-fold greater when OKP cells were treated with dexamethasone. These data suggest that the glucocorticoid-mediated increase in Na+/H+ antiporter activity is due to an increase in NHE-3 gene transcription.
Baum
M
M
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, USA.
Amemiya
M
M
Dwarakanath
V
V
Alpern
R J
RJ
Moe
O W
OW
D000818:Animals; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D004355:Drug Stability; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D009893:Opossums; D012333:RNA, Messenger / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics*; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*
D012333:RNA, Messenger; D017923:Sodium-Hydrogen Exchangers; D003907:Dexamethasone