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Na+-dependent transporters mediate HCO3-salvage across the luminal membrane of the main pancreatic duct

Authors
 Min Goo Lee  ;  Wooin Ahn  ;  Joo Young Choi  ;  Xiang Luo  ;  Jeong Taeg Seo  ;  Patrick J. Schultheis  ;  Gary E. Shull  ;  Kyung Hwan Kim  ;  Shmuel Muallem 
Citation
 Journal of Clinical Investigation, Vol.105(11) : 1651-1658, 2000 
Journal Title
 Journal of Clinical Investigation 
ISSN
 0021-9738 
Issue Date
2000
Abstract
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 μM of the amiloride analogue HOE 694, consistent with expression of NHE1, whereas the luminal activity required 50 μM 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 ∼45%. Notably, the remaining luminal Na+-dependent H+ efflux in ducts from NHE3–/– mice was inhibited by 50 μM HOE 694. Hence, ∼55% of luminal H+ efflux (or HCO3– 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 HCO3– to produce a pancreatic juice that is poor in HCO3– and rich in Cl– during basal secretion. Inhibition of the transporters during stimulated secretion aids in producing the HCO3–-rich pancreatic juice.
Files in This Item:
T200002478.pdf Download
DOI
10.1172/JC9260
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Hwan(김경환)
Seo, Jeong Taeg(서정택) ORCID logo https://orcid.org/0000-0003-2697-0251
Lee, Min Goo(이민구) ORCID logo https://orcid.org/0000-0001-7436-012X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/171686
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