Multiple acid-base and electrolyte disturbances upregulate NBCn1, NBCn2, IRBIT and L-IRBIT in the mTAL.
Multiple acid-base and electrolyte disturbances upregulate NBCn1, NBCn2, IRBIT and L-IRBIT in the mTAL.
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多种酸碱和电解质紊乱上调 mTAL 中 NBCn1、NBCn2、IRBIT 和 L-IRBIT
DOI：
10.1113/jp279009
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发表时间：
2020-08
期刊：
影响因子：
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通讯作者：
Chen LM
中科院分区：
文献类型：
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作者：
Wang JL;Wang XY;Wang DK;Parker MD;Musa-Aziz R;Popple J;Guo YM;Min TX;Xia T;Tan M;Liu Y;Boron WF;Chen LM
髓质粗升支（mTAL）在尿酸和NaCl排泄中起关键作用。NBCn 1和NBCn 2存在于基底外侧mTAL中，其中NBCn 1促进NH 4+分流。伊尔比特和L-伊尔比特（IRBIT）是某些酸碱转运蛋白的两种强有力的激活剂。本研究采用免疫印迹和免疫荧光技术检测了多种酸碱和电解质紊乱对大鼠肾脏NBCn 1、NBCn 2和IRBITs表达的影响。我们还利用电生理学方法研究了IRBIT对爪蟾卵母细胞NBCn 1和NBCn 2的功能影响。NH 4Cl诱导的代谢性酸中毒（MAc）显著增加大鼠肾脏外髓质（OM）中NBCn 1和NBCn 2的蛋白表达。令人惊讶的是，NaHCO 3诱导的代谢紊乱（MAlk）和高盐饮食（HSD）也增加了NBCn 1和NBCn 2的表达（NaHCO 3> HSD的影响）。此外，所有三种挑战通常增加IRBIT的OM表达。在非洲爪蟾卵母细胞中，IRBIT显著增加NBCn 1和NBCn 2的活性。我们认为，基底外侧NBCn 1和NBCn 2以及mTAL中的IRBIT的上调：（1）通过增加基底外侧HCO 3 −摄取来中和MAc期间的顶端NH 4+摄取，从而促进NH 4+分流;（2）通过对抗基底外侧阴离子交换剂AE 2的HCO 3 −流出，抑制MAlk期间的HCO 3 −重吸收;（3）在HSD过程中，通过AE 2介导NaCl净回流到mTAL细胞，抑制NaCl重吸收。因此，NBCn 1，NBCn 2和IRBIT是多个肾脏转运过程的调节途径的连接点。
The medullary thick ascending limb (mTAL) plays a key role in urinary acid and NaCl excretion. NBCn1 and NBCn2 are present in the basolateral mTAL, where NBCn1 promotes NH4+ shunting. IRBIT and L-IRBIT (the IRBITs) are two powerful activators of certain acid-base transporters. Here we use western blotting and immunofluorescence to examine the effects of multiple acid-base and electrolyte disturbances on expression of NBCn1, NBCn2 and the IRBITs in rat kidney. We also use electrophysiology to examine the functional effects of IRBITs on NBCn1 And NBCn2 in Xenopus oocytes. NH4Cl-induced metabolic acidosis (MAc) substantially increases protein expression of NBCn1 and NBCn2 in the outer medulla (OM) of rat kidney. Surprisingly, NaHCO3-induced metabolic alkalosis (MAlk) and high-salt diet (HSD) also increase expression of NBCn1 and NBCn2 (effect of NaHCO3 > HSD). Moreover, all three challenges generally increase OM expression of the IRBITs. In Xenopus oocytes, the IRBITs substantially increase the activities of NBCn1 and NBCn2. We propose that upregulation of basolateral NBCn1 and NBCn2 plus the IRBITs in the mTAL: (1) promotes NH4+ shunting by increasing basolateral HCO3− uptake to neutralize apical NH4+ uptake during MAc; (2) inhibits HCO3− reabsorption during MAlk by opposing HCO3− efflux via the basolateral anion exchanger AE2; and (3) inhibits NaCl reabsorption by mediating (with AE2) net NaCl backflux into the mTAL cell during HSD. Thus, NBCn1, NBCn2 and the IRBITs are at the nexus of the regulatory pathways for multiple renal transport processes.