Regulation of expression of the SN1 transporter during renal adaptation to chronic metabolic acidosis in rats.
During chronic metabolic acidosis, renal glutamine utilization increases markedly. We studied the expression of the system N1 (SN1) amino acid transporter in the kidney during chronic ammonium chloride acidosis in rats. Acidosis caused a 10-fold increase in whole kidney SN1 mRNA level and a 100-fold increase in the cortex. Acidosis increased Na(+)-dependent glutamine uptake into basolateral and brush-border membrane vesicles (BLMV and BBMV, respectively) isolated from rat cortex (BLMV, 219 +/- 66 control vs. 651 +/- 180 pmol. mg(-1). min(-1) acidosis; BBMV, 1,112 +/- 189 control vs. 1,652 +/- 148 pmol. mg(-1). min(-1) acidosis, both P < 0.05). Na(+)-independent uptake was unchanged by acidosis in BLMV and BBMV. The acidosis-induced increase in Na(+)-dependent glutamine uptake was eliminated by histidine, confirming transport by system N. SN1 protein was detected only in BLMV and BBMV from acidotic rats. After recovery from acidosis, SN1 mRNA and protein and Na(+)-dependent glutamine uptake activity rapidly returned to control levels. These data provide evidence that regulation of expression of the SN1 amino acid transporter is part of the renal homeostatic response to acid-base imbalance.
Karinch
Anne M
AM
Department of Surgery, Milton S. Hershey Medical Center, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Lin
Cheng-Mao
CM
Wolfgang
Christopher L
CL
Pan
Ming
M
Souba
Wiley W
WW
D000138:Acidosis / Q000378:metabolism* / Q000503:physiopathology; D000222:Adaptation, Physiological / Q000502:physiology*; D026921:Amino Acid Transport Systems, Neutral; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002908:Chronic Disease; D015870:Gene Expression / Q000502:physiology; D005973:Glutamine / Q000378:metabolism; D007672:Kidney Cortex / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D008871:Microvilli / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D026921:Amino Acid Transport Systems, Neutral; D026901:Membrane Transport Proteins; D000644:Quaternary Ammonium Compounds; D012333:RNA, Messenger; C403222:system N protein 1; D005973:Glutamine; D000641:Ammonia