PMID- 10362779
OWN - NLM
STAT- MEDLINE
DCOM- 19990722
LR  - 20181127
IS  - 0002-9513 (Print)
IS  - 0002-9513 (Linking)
VI  - 276
IP  - 6
DP  - 1999 Jun
TI  - Characterization of Na+/HCO-3 cotransporter isoform NBC-3.
PG  - F903-13
LID - 10.1152/ajprenal.1999.276.6.F903 [doi]
AB  - Na+-HCO-3 cotransporters mediate the transport of HCO-3 into or out of the cell. 
      Two Na+-HCO-3 cotransporters (NBC) have been identified previously, which are
      referred to as NBC-1 and NBC-2. A cDNA library from uninduced human NT-2 cells
      was screened with an NBC-2 cDNA probe. Several clones were identified and
      isolated. Sequence analysis of these clones identified a partial coding region (2
      kb) of a novel NBC (called here NBC-3), which showed 53% and 72% identity with
      NBC-1 and NBC-2, respectively. Northern blot analysis revealed that NBC-3 encodes
      a 4.4-kb mRNA with a tissue distribution pattern distinct from NBC-1 and NBC-2.
      NBC-3 is highly expressed in brain and spinal column, with moderate levels in
      trachea, thyroid, and kidney. In contrast with NBC-1, NBC-3 shows low levels of
      expression in pancreas and kidney cortex. In the kidney, NBC-3 expression is
      predominantly limited to the medulla. Cultured mouse inner medullary collecting
      duct (mIMCD-3) cells showed high levels of NBC-1 and low levels of NBC-3 mRNA
      expression. Subjecting the mutagenized mIMCD-3 cells to sublethal acid stress
      decreased the mRNA expression of NBC-1 by approximately 90% but increased the
      Na+-dependent HCO-3 cotransport activity by approximately 7-fold (as assayed by
      DIDS-sensitive, Na+-dependent, HCO-3-mediated intracellular pH recovery). This
      increase was associated with approximately 5.5-fold enhancement of NBC-3 mRNA
      levels. NBC showed significant affinity for Li+ in the mutant but not the parent 
      mIMCD-3 cells. On the basis of the widespread distribution of NBC-3, we propose
      that this isoform is likely involved in cell pH regulation by transporting HCO-3 
      from blood to the cell. We further propose that enhanced expression of NBC-3 in
      severe acid stress could play an important role in cell survival by mediating the
      influx of HCO-3 into the cells.
FAU - Amlal, H
AU  - Amlal H
AD  - Division of Nephrology, Department of Internal Medicine, University of
      Cincinnati, Cincinnati, Ohio 45267-0585, USA.
FAU - Burnham, C E
AU  - Burnham CE
FAU - Soleimani, M
AU  - Soleimani M
LA  - eng
SI  - GENBANK/AF107099
GR  - R01-DK-46789/DK/NIDDK NIH HHS/United States
GR  - R01-DK-52821/DK/NIDDK NIH HHS/United States
GR  - R01-DK-54430/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Physiol
JT  - The American journal of physiology
JID - 0370511
RN  - 0 (Acids)
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA, Complementary)
RN  - 0 (RNA, Messenger)
RN  - 0 (SLC4A8 protein, human)
RN  - 0 (Sodium-Bicarbonate Symporters)
SB  - IM
EIN - Am J Physiol 1999 Sep;277(3 Pt 2):followi
MH  - Acids/pharmacology
MH  - Amino Acid Sequence/genetics
MH  - Animals
MH  - Base Sequence/genetics
MH  - Brain/metabolism
MH  - Carrier Proteins/*genetics/*metabolism
MH  - Cell Line
MH  - DNA, Complementary/genetics
MH  - Humans
MH  - Kidney/metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Molecular Sequence Data
MH  - RNA, Messenger/metabolism
MH  - Sodium-Bicarbonate Symporters
MH  - Spinal Cord/metabolism
MH  - Tissue Distribution/physiology
EDAT- 1999/06/11 00:00
MHDA- 1999/06/11 00:01
CRDT- 1999/06/11 00:00
PHST- 1999/06/11 00:00 [pubmed]
PHST- 1999/06/11 00:01 [medline]
PHST- 1999/06/11 00:00 [entrez]
AID - 10.1152/ajprenal.1999.276.6.F903 [doi]
PST - ppublish
SO  - Am J Physiol. 1999 Jun;276(6):F903-13. doi: 10.1152/ajprenal.1999.276.6.F903.