Renal expression of the ammonia transporters, Rhbg and Rhcg, in response to chronic metabolic acidosis.
Chronic metabolic acidosis induces dramatic increases in net acid excretion that are predominantly due to increases in urinary ammonia excretion. The current study examines whether this increase is associated with changes in the expression of the renal ammonia transporter family members, Rh B glycoprotein (Rhbg) and Rh C glycoprotein (Rhcg). Chronic metabolic acidosis was induced in Sprague-Dawley rats by HCl ingestion for 1 wk; control animals were pair-fed. After 1 wk, metabolic acidosis had developed, and urinary ammonia excretion increased significantly. Rhcg protein expression was increased in both the outer medulla and the base of the inner medulla. Intercalated cells in the outer medullary collecting duct (OMCD) and in the inner medullary collecting duct (IMCD) in acid-loaded animals protruded into the tubule lumen and had a sharp, discrete band of apical Rhcg immunoreactivity, compared with a flatter cell profile and a broad band of apical immunolabel in control kidneys. In addition, basolateral Rhcg immunoreactivity was observed in both control and acidotic kidneys. Cortical Rhcg protein expression and immunoreactivity were not detectably altered. Rhcg mRNA expression was not significantly altered in the cortex, outer medulla, or inner medulla by chronic metabolic acidosis. Rhbg protein and mRNA expression were unchanged in the cortex, outer and inner medulla, and no changes in Rhbg immunolabel were evident in these regions. We conclude that chronic metabolic acidosis increases Rhcg protein expression in intercalated cells in the OMCD and in the IMCD, where it is likely to mediate an important role in the increased urinary ammonia excretion.
Seshadri
Ramanathan M
RM
University of Florida College of Medicine, P. O. Box 100224, Gainesville, FL 32610-0224, USA.
Klein
Janet D
JD
Kozlowski
Shelley
S
Sands
Jeff M
JM
Kim
Young-Hee
YH
Han
Ki-Hwan
KH
Handlogten
Mary E
ME
Verlander
Jill W
JW
Weiner
I David
ID
D000141:Acidosis, Renal Tubular / Q000139:chemically induced / Q000378:metabolism*; D000641:Ammonia / Q000378:metabolism*; D000818:Animals; D027682:Cation Transport Proteins / Q000378:metabolism*; D004573:Electrolytes / Q000097:blood / Q000652:urine; D007668:Kidney / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000378:metabolism* / Q000502:physiology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D027682:Cation Transport Proteins; D004573:Electrolytes; D008562:Membrane Glycoproteins; C508142:Rh type B glycoprotein, rat; C508143:Rh type C glycoprotein, rat; D000641:Ammonia