PMID- 12372813
OWN - NLM
STAT- MEDLINE
DCOM- 20021112
LR  - 20200930
IS  - 0363-6143 (Print)
IS  - 0363-6143 (Linking)
VI  - 283
IP  - 5
DP  - 2002 Nov
TI  - The functional and physical relationship between the DRA bicarbonate transporter 
      and carbonic anhydrase II.
PG  - C1522-9
AB  - COOH-terminal cytoplasmic tails of chloride/bicarbonate anion exchangers (AE) 
      bind cytosolic carbonic anhydrase II (CAII) to form a bicarbonate transport 
      metabolon, a membrane protein complex that accelerates transmembrane bicarbonate 
      flux. To determine whether interaction with CAII affects the downregulated in 
      adenoma (DRA) chloride/bicarbonate exchanger, anion exchange activity of 
      DRA-transfected HEK-293 cells was monitored by following changes in intracellular 
      pH associated with bicarbonate transport. DRA-mediated bicarbonate transport 
      activity of 18 +/- 1 mM H+ equivalents/min was inhibited 53 +/- 2% by 100 mM of 
      the CAII inhibitor, acetazolamide, but was unaffected by the membrane-impermeant 
      carbonic anhydrase inhibitor, 
      1-[5-sulfamoyl-1,3,4-thiadiazol-2-yl-(aminosulfonyl-4-phenyl)]-2,6-dimethyl-4-phenyl-pyridinium 
      perchlorate. Compared with AE1, the COOH-terminal tail of DRA interacted weakly 
      with CAII. Overexpression of a functionally inactive CAII mutant, V143Y, reduced 
      AE1 transport activity by 61 +/- 4% without effect on DRA transport activity (105 
      +/- 7% transport activity relative to DRA alone). We conclude that cytosolic CAII 
      is required for full DRA-mediated bicarbonate transport. However, DRA differs 
      from other bicarbonate transport proteins because its transport activity is not 
      stimulated by direct interaction with CAII.
FAU - Sterling, Deborah
AU  - Sterling D
AD  - Canadian Institutes of Health Research Membrane Protein Research Group, 
      Department of Physiology, University of Alberta, Edmonton, Alberta, Canada T6G 
      2H7.
FAU - Brown, Nathan J D
AU  - Brown NJ
FAU - Supuran, Claudiu T
AU  - Supuran CT
FAU - Casey, Joseph R
AU  - Casey JR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Antiporters)
RN  - 0 (Bicarbonates)
RN  - 0 (Carbonic Anhydrase Inhibitors)
RN  - 0 (Carrier Proteins)
RN  - 0 (Chloride-Bicarbonate Antiporters)
RN  - 0 (Chlorides)
RN  - 0 (Membrane Proteins)
RN  - 0 (SLC26A3 protein, human)
RN  - 0 (Sulfate Transporters)
RN  - EC 4.2.1.- (Carbonic Anhydrase II)
RN  - O3FX965V0I (Acetazolamide)
SB  - IM
MH  - Acetazolamide/pharmacology
MH  - Adenoma/metabolism
MH  - *Antiporters
MH  - Bicarbonates/*metabolism
MH  - Carbonic Anhydrase II/antagonists & inhibitors/*metabolism
MH  - Carbonic Anhydrase Inhibitors/pharmacology
MH  - Carrier Proteins/genetics/*metabolism
MH  - Cell Line
MH  - Cell Membrane/metabolism
MH  - Chloride-Bicarbonate Antiporters
MH  - Chlorides/metabolism
MH  - Down-Regulation
MH  - Humans
MH  - Membrane Proteins/genetics/*metabolism
MH  - Protein Binding/physiology
MH  - Sulfate Transporters
MH  - Transfection
EDAT- 2002/10/10 04:00
MHDA- 2002/11/26 04:00
CRDT- 2002/10/10 04:00
PHST- 2002/10/10 04:00 [pubmed]
PHST- 2002/11/26 04:00 [medline]
PHST- 2002/10/10 04:00 [entrez]
AID - 10.1152/ajpcell.00115.2002 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2002 Nov;283(5):C1522-9. doi: 
      10.1152/ajpcell.00115.2002.