An autocrine role for endothelin-1 in the regulation of proximal tubule NHE3.
BACKGROUND
Chronic metabolic acidosis leads to an increase in NHE3 activity that is mediated by endothelin-1 (ET-1) expression and activation of the proximal tubule endothelin B receptor. Chronic metabolic acidosis increases preproET-1 mRNA abundance in kidney cortex, but the cell responsible has not been identified.


METHODS
PreproET-1 mRNA abundance was quantified by competitive reverse transcription-polymerase chain reaction (RT-PCR) on tissue harvested from control rats or rats in which chronic metabolic acidosis was induced by addition of NH(4)Cl to the drinking water.


RESULTS
Chronic metabolic acidosis leads to an increase in preproET-1 mRNA expression in kidney cortex, proximal tubules, and glomeruli. The increase in preproET-1 expression correlates with the decrease in blood [HCO3(-)]. ET-1 expression is also increased by acidosis in abdominal aorta, but not in cardiac muscle.


CONCLUSIONS
In the renal proximal tubule, chronic metabolic acidosis induces an increase in preproET-1 expression, providing a mechanism for autocrine regulation of proximal tubule NHE3 activity. This response is not unique to the proximal tubule cell, but is also not ubiquitous.
Licht
Christoph
C
Department of Internal Medicine and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Laghmani
Kamel
K
Yanagisawa
Masashi
M
Preisig
Patricia A
PA
Alpern
Robert J
RJ
D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000378:metabolism; D019898:Autocrine Communication / Q000502:physiology*; D002908:Chronic Disease; D019332:Endothelin-1 / Q000235:genetics / Q000502:physiology*; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*
D019332:Endothelin-1; D012333:RNA, Messenger; C000613387:Slc9a3 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers