Document Detail

Na(+)-dependent transporters mediate HCO(3)(-) salvage across the luminal membrane of the main pancreatic duct.
MedLine Citation:
PMID:  10841524     Owner:  NLM     Status:  MEDLINE    
To study the roles of Na(+)-dependent H(+) transporters, we characterized H(+) efflux mechanisms in the pancreatic duct in wild-type, NHE2(-/-), and NHE3(-/-) mice. The pancreatic duct expresses NHE1 in the basolateral membrane, and NHE2 and NHE3 in the luminal membrane, but does not contain NHE4 or NHE5. Basolateral Na(+)-dependent H(+) efflux in the microperfused duct was inhibited by 1.5 microM of the amiloride analogue HOE 694, consistent with expression of NHE1, whereas the luminal activity required 50 microM HOE 694 for effective inhibition, suggesting that the efflux might be mediated by NHE2. However, disruption of NHE2 had no effect on luminal transport, while disruption of the NHE3 gene reduced luminal Na(+)-dependent H(+) efflux by approximately 45%. Notably, the remaining luminal Na(+)-dependent H(+) efflux in ducts from NHE3(-/-) mice was inhibited by 50 microM HOE 694. Hence, approximately 55% of luminal H(+) efflux (or HCO(3)(-) influx) in the pancreatic duct is mediated by a novel, HOE 694-sensitive, Na(+)-dependent mechanism. H(+) transport by NHE3 and the novel transporter is inhibited by cAMP, albeit to different extents. We propose that multiple Na(+)-dependent mechanisms in the luminal membrane of the pancreatic duct absorb Na(+) and HCO(3)(-) to produce a pancreatic juice that is poor in HCO(3)(-) and rich in Cl(-) during basal secretion. Inhibition of the transporters during stimulated secretion aids in producing the HCO(3)(-)-rich pancreatic juice.
M G Lee; W Ahn; J Y Choi; X Luo; J T Seo; P J Schultheis; G E Shull; K H Kim; S Muallem
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  105     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2000 Jun 
Date Detail:
Created Date:  2000-08-24     Completed Date:  2000-08-24     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1651-8     Citation Subset:  AIM; IM    
Department of Pharmacology, College of Medicine, Yonsei University, Seoul, Korea.
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MeSH Terms
Bicarbonates / metabolism*
Chlorides / metabolism
Cyclic AMP / physiology
Pancreatic Ducts / metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Sodium-Hydrogen Antiporter / analysis,  physiology*
Grant Support
Reg. No./Substance:
0/Bicarbonates; 0/Chlorides; 0/Slc9a2 protein, mouse; 0/Sodium-Hydrogen Antiporter; 0/growth factor-activatable Na-H exchanger NHE-1; 0/sodium-hydrogen exchanger 3; 60-92-4/Cyclic AMP

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