Na+-dependent transporters mediate HCO3- salvage across the luminal membrane of the main pancreatic duct
Na+-dependent transporters mediate HCO3- salvage across the luminal membrane of the main pancreatic duct
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DOI：
10.1172/jci9207
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发表时间：
2000-06-01
影响因子：
15.9
通讯作者：
Muallem, S
中科院分区：
文献类型：
--
作者：
Lee, MG;Ahn, W;Muallem, S
为了研究Na+依赖性H+转运蛋白的作用，我们对野生型、NHE 2（-/-）和NHE 3（-/-）小鼠胰管中的H+流出机制进行了表征。胰管在基底外侧膜中表达NHE 1，在管腔膜中表达NHE 2和NHE 3，但不含NHE 4或NHE 5。1.5 μ M阿米洛利类似物HOE 694抑制微灌注导管中的基底外侧Na+依赖性H+流出，与NHE 1的表达一致，而管腔活性需要50 μ M HOE 694才能有效抑制，表明流出可能由NHE 2介导。然而，NHE 2的破坏对管腔运输没有影响，而NHE 3基因的破坏减少了管腔Na+依赖性H+流出，减少幅度接近45%。值得注意的是，50 μ M HOE 694抑制了NHE 3-/-小鼠导管中剩余的管腔Na+依赖性H+外排。因此，胰管中55%的管腔H+外排（或HCO 3-内流）由一种新的HOE 694敏感性Na+依赖性机制介导。NHES和新型转运蛋白的H+转运受到cAMP的抑制，尽管程度不同。我们建议，多个Na+依赖性机制的胰管腔膜吸收Na+和HCO 3-产生的胰液是穷人在HCO 3-和丰富的Cl-在基础分泌。在刺激分泌期间抑制转运蛋白有助于产生富含HCO 3的胰液。
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.