Function and structure of H-K-ATPase in the kidney.
Function and structure of H-K-ATPase in the kidney.
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肾脏中 H-K-ATP 酶的功能和结构。
DOI：
10.1152/ajprenal.1995.269.1.f1
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Smolka,AJ
中科院分区：
文献类型：
--
作者：
Wingo,CS;Smolka,AJ
本综述总结了最近的功能和结构的证据表明，肾脏拥有至少一个，可能不止一个异构体的质子和钾激活的腺苷三磷酸酶（H-K-ATP酶）。功能研究已经详细研究了腔酸化和K/Rb吸收的外髓集合管（OMCD）从内部条纹，一个高容量的远端网站的尿酸化的机制。这些研究表明，质子分泌的机制，在这段是类似的模型提出的胃酸分泌。具体而言，H-K-ATP酶抑制剂或管腔钾去除对净碳酸氢盐（HCO 3）吸收的深刻影响表明H-K泵在OMCD管腔酸化中发挥重要作用。纳摩尔浓度的巴弗洛霉素A1特异性抑制空泡型H-ATP酶，其对HCO 3净吸收的影响显著小于H-K-ATP酶抑制剂，这一发现进一步支持了H-K-ATP酶的重要性。对灌注的内髓集合管（IMCD）和培养的IMCD细胞的研究也表明H-K-ATP酶在IMCD的管腔酸化中起重要作用。从皮质CD和OMCD的研究中已经积累了证据，表明在K-充分和K-限制条件下，H-K-ATP酶介导的腔质子分泌的机制不同。在钾补充中，由泵输送的腔钾离子通过Ba敏感机制再循环回到腔中。然而，在K限制中，H-K-ATP酶的机制涉及腔质子分泌和K吸收，其对腔Ba不敏感，并且由此推断，顶端K再循环。此外，在K限制，K/Rb吸收抑制基底外侧Ba，表明泵操作重新吸收K/Rb跨上皮。本文综述的结构证据表明，哺乳动物肾脏中存在与胃和假定的结肠H-K-ATP酶α亚基和胃H-K-ATP酶β亚基的mRNA相同或高度同源的mRNA。通过原位杂交定位这些成绩单表明，在皮质和髓质CD，CD的主细胞和IMCD细胞的闰细胞中的胃α-和β-亚基mRNA。在转基因小鼠中的其他研究表明，H-K-ATP酶β亚基基因上游的调控序列指导胃壁细胞和肾CD中的转录。（400字处截断摘要）
The present review summarizes recent functional and structural evidence indicating that the kidney possesses at least one and probably more than one isoform of a proton- and potassium-activated adenosinetriphosphatase (H-K-ATPase). Functional studies have examined in detail the mechanism of luminal acidification and K/Rb absorption by the outer medullary collecting duct (OMCD) from the inner stripe, a high-capacity distal site of urinary acidification. These studies indicate that the mechanism of proton secretion in this segment is similar to a model proposed for gastric acid secretion. Specifically, the profound effect of H-K-ATPase inhibitors or luminal K removal on net bicarbonate (HCO3) absorption indicates a major role for an H-K pump in luminal acidification by the OMCD. The importance of an H-K-ATPase is further supported by the finding that nanomolar concentrations of bafilomycin A1, which specifically inhibit vacuolar-type H-ATPase, have significantly smaller effects on net HCO3 absorption than do H-K-ATPase inhibitors. Studies on the perfused inner medullary collecting duct (IMCD) and cultured IMCD cells also suggest a significant role for H-K-ATPase in luminal acidification by the IMCD. Evidence has accrued from studies in the cortical CD and OMCD that the mechanism of H-K-ATPase-mediated luminal proton secretion differs under K-replete and K-restricted conditions. In K repletion, luminal K ions transported by the pump recycle back into the lumen by a Ba-sensitive mechanism. However, in K restriction, the mechanism of the H-K-ATPase involves luminal proton secretion and K absorption that is insensitive to luminal Ba and, by inference, apical K recycling. Moreover, in K restriction, K/Rb absorption is inhibited by basolateral Ba, indicating that the pump operates to reabsorb K/Rb across the epithelium. The structural evidence reviewed here indicates the presence of mRNA within the mammalian kidney that is either identical or highly homologous to mRNAs for gastric and putative colonic H-K-ATPase alpha-subunits and gastric H-K-ATPase beta-subunit. Localization of these transcripts by in situ hybridization demonstrates gastric alpha- and beta-subunit mRNAs in intercalated cells of both the cortical and medullary CD, principal cells of the CD, and IMCD cells. Additional studies in transgenic mice indicate that regulatory sequences upstream to the H-K-ATPase beta-subunit gene direct transcription in both gastric parietal cells and the renal CD.(ABSTRACT TRUNCATED AT 400 WORDS)