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

被引:48
作者
Lee, MG
Ahn, W
Choi, JY
Luo, X
Seo, JT
Schultheis, PJ
Shull, GE
Kim, KH
Muallem, S
机构
[1] Yonsei Univ, Coll Med, Dept Pharmacol, Seoul 120752, South Korea
[2] Univ Texas, SW Med Ctr, Dept Physiol, Dallas, TX 75235 USA
[3] Yonsei Univ, Coll Dent, Dept Oral Biol, Seoul 120749, South Korea
[4] Univ Cincinnati, Sch Med, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45221 USA
关键词
D O I
10.1172/JCI9207
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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 mu M of the amiloride analogue HOE 694, consistent with expression of NHE1, whereas the luminal activity required 50 mu M 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 similar to 45%. Notably, the remaining luminal Na+-dependent H+ efflux in ducts from NHE3-/- mice was inhibited by 50 mu M HOE 694. Hence, similar to 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 NHES 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.
引用
收藏
页码:1651 / 1658
页数:8
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