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Hypercapnia Upregulates Expression of the NH 3 /NH 4 + Transporter Rhbg in the Kidney
Author(s) -
Nakhoul Nazih L,
HeringSmith Kathleen,
Hamm L. Lee,
Islam M. Toriqul,
AbdulnourNakhoul Solange
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb816
Subject(s) - acidosis , hypercapnia , respiratory acidosis , intracellular ph , excretion , kidney , endocrinology , medicine , chemistry , kidney disease , intracellular , biochemistry
Hypercapnia occurs in patients with acute and chronic lung diseases such as chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome and is a major cause of increased mortality in hospitalized sick patients with COPD or cystic fibrosis. The kidneys compensate for respiratory acidosis by increasing urinary acid excretion (predominantly as NH 3 /NH 4 + ) and de‐novo production of HCO 3 − . The mechanisms responsible for increased renal NH 3 /NH 4 + excretion are not well known. In this study, we investigated whether the renal NH 3 /NH 4 + transporters, Rhbg and Rhcg, are affected by hypercapnia. Using H + ‐selective microelectrodes, we showed that CO 2 caused a faster intracellular pH (pH i ) decrease in oocytes expressing Rhbg as compared to H 2 O‐injected oocytes (−47 vs −17 × 10 −4 pH/sec) indicating enhanced CO 2 transport by Rhbg. Using In‐Cell Western, we showed that inner medullary collecting duct IMCD3 cells (that express Rhbg and Rhcg) grown on semi‐permeable membranes had a dramatic increase in Rhbg expression after 48 hours exposure to 20% CO 2 . Rhcg expression followed a similar pattern but the proportional increase in expression was smaller. In a series of in‐vivo experiments in mice, we induced respiratory acidosis by placing the mice in special chambers where the breathing gas mixtures were 8% CO 2 (balance 21% O 2 & 71% N 2 ). Control group breathed normal air. After 4 days, the kidneys were extracted and Rhbg protein expression was assessed by Western analysis. Our data indicate that in hypercapnia Rhbg expression was increased by 23%, compared to control (n=5, p<0.05). These results indicate that CO 2 is transported by Rhbg and that respiratory acidosis upregulated Rhbg expression. Enhanced cellular CO 2 transport, due to elevated CO 2 in respiratory acidosis and/or changes in acid‐base status, may be responsible for upregulating expression of the renal NH 3 /NH 4 + transporter Rhbg. Support or Funding Information VA Merit grant, NIH‐RO1 and Tulane Institutional Fund