Chronic regulation of the Na/H antiporter.
This review focuses on studies from our laboratory investigating the mechanisms of chronic regulation of the Na/H antiporter in renal and nonrenal cells. Tissue culture provides an ideal tool for investigating this problem because it avoids many complicating effects that would occur in an intact animal during a chronic study. Chronic decreases in extracellular fluid pH cause an increase in Na/H antiporter activity that is dependent on protein synthesis and associated with an increase in NHE-1 (isoform of the sodium-hydrogen antiporter) mRNA abundance. This effect is associated with acid-induced increases in a number of immediate early genes, including c-fos, c-jun, junB, and egr-1. In primary cultures of rabbit proximal tubule cells, activation of protein kinase C for 2 hours causes an increase in Na/H antiporter activity that persists 24 hours later, is dependent on transcription and translation, and is associated with an increase in NHE-1 mRNA abundance. Chronic activation of protein kinase A in opossum kidney (OKP) cells causes an increase in Na/H antiporter activity that persists 16 to 20 hours later and is dependent on protein synthesis. This latter effect is of particular interest because it is opposite in direction to the acute inhibitory effect of protein kinase A on the Na/H antiporter in these cells.
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-8856.
R J
RJ
Alpern
Y
Y
Yamaji
A
A
Cano
S
S
Horie
R T
RT
Miller
O W
OW
Moe
P A
PA
Preisig
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006859:Hydrogen / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D011494:Protein Kinases / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers
D002352:Carrier Proteins; D017923:Sodium-Hydrogen Exchangers; D006859:Hydrogen; D012964:Sodium; D011494:Protein Kinases