Upregulation of the secretory-type Na(+)/K(+)/2Cl(-)-cotransporter in the kidney by metabolic acidosis and dehydration in rats.
The functional role and mechanisms of regulation of the Na(+)/K(+)/2Cl(-)-cotransporter NKCC1 in the kidney have not yet been clarified. NKCC1 mRNA and protein expression in control rats, rats with dehydration (2 d), and rats with metabolic acidosis (NH(4)Cl in the food for 6 to 7 d) was examined using reverse transcription-PCR and Western blotting. In contrast to the abundant NKCC1 mRNA expression in the terminal inner medullary collecting ducts in mice, expression was found to be most abundant in the outer medullary collecting ducts (OMCD) in rats. Dehydration and metabolic acidosis increased NKCC1 mRNA expression three- to fivefold not only in the OMCD but also in the cortical collecting ducts and inner medullary collecting ducts. Dehydration and metabolic acidosis increased NKCC1 protein expression twofold in the membrane fraction from the outer medulla. NKCC1 protein expression was observed not in the microdissected medullary thick ascending limbs but in the OMCD, and it was stimulated twofold by dehydration and metabolic acidosis. Incubation of OMCD in low-pH medium increased NKCC1 mRNA expression. In summary, NKCC1 mRNA and protein expression is upregulated with dehydration and metabolic acidosis. NKCC1 may play an important role in adaptation to these physiologic conditions. Low pH and possibly hypertonicity stimulate NKCC1 mRNA expression in OMCD.
Ikebe
Mika
M
Third Department of Internal Medicine, Kumamoto University School of Medicine, Kumamoto, Japan.
Nonoguchi
Hiroshi
H
Third Department of Internal Medicine, Kumamoto University School of Medicine, Kumamoto, Japan.
Nakayama
Yushi
Y
Third Department of Internal Medicine, Kumamoto University School of Medicine, Kumamoto, Japan.
Tashima
Yuka
Y
Third Department of Internal Medicine, Kumamoto University School of Medicine, Kumamoto, Japan.
Tomita
Kimio
K
Third Department of Internal Medicine, Kumamoto University School of Medicine, Kumamoto, Japan.
D000138:Acidosis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D003681:Dehydration / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D017136:Ion Transport; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D011188:Potassium / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012964:Sodium / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters; D014018:Tissue Distribution
D002352:Carrier Proteins; D002712:Chlorides; D017931:DNA Primers; D012333:RNA, Messenger; D028021:Sodium-Potassium-Chloride Symporters; D012964:Sodium; D011188:Potassium