PMID- 20150244
OWN - NLM
STAT- MEDLINE
DCOM- 20100506
LR  - 20211020
IS  - 1522-1547 (Electronic)
IS  - 0193-1857 (Print)
IS  - 0193-1857 (Linking)
VI  - 298
IP  - 5
DP  - 2010 May
TI  - Putative anion transporter-1 (Pat-1, Slc26a6) contributes to intracellular pH 
      regulation during H+-dipeptide transport in duodenal villous epithelium.
PG  - G683-91
LID - 10.1152/ajpgi.00293.2009 [doi]
AB  - The majority of dietary amino acids are absorbed via the H(+)-di-/tripeptide 
      transporter Pept1 of the small intestine. Proton influx via Pept1 requires 
      maintenance of intracellular pH (pH(i)) to sustain the driving force for peptide 
      absorption. The apical membrane Na(+)/H(+) exchanger Nhe3 plays a major role in 
      minimizing epithelial acidification during H(+)-di-/tripeptide absorption. 
      However, the contributions of HCO(3)(-)-dependent transporters to this process 
      have not been elucidated. In this study, we investigate the role of putative 
      anion transporter-1 (Pat-1), an apical membrane anion exchanger, in epithelial 
      pH(i) regulation during H(+)-peptide absorption. Using wild-type (WT) and 
      Pat-1(-) mice, Ussing chambers were employed to measure the short-circuit current 
      (I(sc)) associated with Pept1-mediated glycyl-sarcosine (Gly-Sar) absorption. 
      Microfluorometry was used to measure pH(i) and Cl(-)/HCO(3)(-) exchange in the 
      upper villous epithelium. In CO(2)/HCO(3)(-)-buffered Ringers, WT small intestine 
      showed significant Gly-Sar-induced I(sc) and efficient pH(i) regulation during 
      pharmacological inhibition of Nhe3 activity. In contrast, epithelial 
      acidification and reduced I(sc) response to Gly-Sar exposure occurred during 
      pharmacological inhibition of Cl(-)/HCO(3)(-) exchange and in the Pat-1(-) 
      intestine. Pat-1 interacts with carbonic anhydrase II (CAII), and studies using 
      CAII(-) intestine or the pharmacological inhibitor methazolamide on WT intestine 
      resulted in increased epithelial acidification during Gly-Sar exposure. Increased 
      epithelial acidification during Gly-Sar exposure also occurred in WT intestine 
      during inhibition of luminal extracellular CA activity. Measurement of 
      Cl(-)/HCO(3)(-) exchange in the presence of Gly-Sar revealed an increased rate of 
      Cl(-)(OUT)/HCO(3)(-)(IN) exchange that was both Pat-1 dependent and CA dependent. 
      In conclusion, Pat-1 Cl(-)/HCO(3)(-) exchange contributes to pH(i) regulation in 
      the villous epithelium during H(+)-dipeptide absorption, possibly by providing a 
      HCO(3)(-) import pathway.
FAU - Simpson, Janet E
AU  - Simpson JE
AD  - Dalton Cardiovascular Research Center, Univ. of Missouri-Columbia, 65211, USA.
FAU - Walker, Nancy M
AU  - Walker NM
FAU - Supuran, Claudiu T
AU  - Supuran CT
FAU - Soleimani, Manoocher
AU  - Soleimani M
FAU - Clarke, Lane L
AU  - Clarke LL
LA  - eng
GR  - DK 48816/DK/NIDDK NIH HHS/United States
GR  - DK 62809/DK/NIDDK NIH HHS/United States
GR  - T32-RR 07004/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100211
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (Antiporters)
RN  - 0 (Bicarbonates)
RN  - 0 (Dipeptides)
RN  - 0 (Slc26a6 protein, mouse)
RN  - 0 (Sulfate Transporters)
RN  - 29816-01-1 (glycylsarcosine)
RN  - EC 4.2.1.- (Carbonic Anhydrase II)
SB  - IM
MH  - Animals
MH  - Antiporters/*physiology
MH  - Bicarbonates/metabolism
MH  - Carbonic Anhydrase II/metabolism
MH  - Dipeptides/*metabolism
MH  - Duodenum/metabolism
MH  - Hydrogen-Ion Concentration
MH  - Mice
MH  - Sulfate Transporters
PMC - PMC2867431
EDAT- 2010/02/13 06:00
MHDA- 2010/05/07 06:00
PMCR- 2011/05/01
CRDT- 2010/02/13 06:00
PHST- 2010/02/13 06:00 [entrez]
PHST- 2010/02/13 06:00 [pubmed]
PHST- 2010/05/07 06:00 [medline]
PHST- 2011/05/01 00:00 [pmc-release]
AID - ajpgi.00293.2009 [pii]
AID - GI-00293-2009 [pii]
AID - 10.1152/ajpgi.00293.2009 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2010 May;298(5):G683-91. doi: 
      10.1152/ajpgi.00293.2009. Epub 2010 Feb 11.