Cantone A, Wang T, Pica A, Simeoni M, Capasso G
Chair of Nephrology, School of Medicine, Second University of Naples, Naples, Italy.
J Nephrol. 2006 Mar-Apr;19 Suppl 9:S121-7.
The kidney is essential in maintaining body acid-base status. Recently, the use of transgenic mice has largely contributed to the understanding of the mechanisms involved. Important issues have been addressed in terms of the function of proteins or their regulation. In the proximal tubule, the role of Na+/HCO3-cotransport has been established, although further studies are needed to understand how its mutations lead to renal disease. Na+/H+ exchange has also been extensively studied, and its role in diuretic and natriuretic responses following an increase in blood pressure has been elucidated. The interaction of other transport proteins, such as the Na+/phosphate cotransporter NaPi II-a, with the Na+/H+ exchanger has also been investigated. In the medullary thick ascending limb of Henle's loop (MTAL), a role for NHE1 in transepithelial HCO3- absorption has been demonstrated: basolateral NHE1 controls the function of apical NHE3. As for the distal nephron, the majority of observations suggest that the regulation of H+-ATPase activity in response to acid-base status is mediated by the trafficking of pumps or pump sub-units, especially for the a4 subunit, rather than changes in subunit expression levels. Furthermore, the function of pendrin, a chloride/anion exchanger, has been assessed in response to changes in acid-base status. Important results have been obtained regarding the regulation of proximal tubule transport by several mechanisms, such as microvilli changes and the inducible and endothelial isoform of nitric oxide synthase (NOS). Finally, the interaction of chloride channels and potassium-chloride cotransporter with proton secretion has been evaluated. These findings highlight the importance of knockout animal models in studying kidney regulation of acid-base balance.
肾脏在维持机体酸碱平衡方面至关重要。近来，转基因小鼠的应用在很大程度上有助于理解其中涉及的机制。在蛋白质功能或其调节方面，一些重要问题已得到探讨。在近端小管中，Na⁺/HCO₃⁻共转运的作用已得到证实，不过仍需进一步研究以了解其突变如何导致肾脏疾病。Na⁺/H⁺交换也已得到广泛研究，并且其在血压升高后利尿和利钠反应中的作用已得到阐明。其他转运蛋白，如Na⁺/磷酸盐共转运体NaPi II - a与Na⁺/H⁺交换体之间的相互作用也已被研究。在亨氏袢髓质厚升支（MTAL）中，已证实NHE1在跨上皮HCO₃⁻吸收中起作用：基底外侧NHE1控制顶端NHE3的功能。至于远端肾单位，大多数观察结果表明，H⁺ - ATP酶活性对酸碱状态的调节是由泵或泵亚基的转运介导的，特别是对于α4亚基，而不是亚基表达水平的变化。此外，已评估了氯/阴离子交换体pendrin在酸碱状态变化时的功能。关于近端小管转运通过几种机制的调节，如微绒毛变化以及一氧化氮合酶（NOS）的诱导型和内皮型，已获得重要结果。最后，已评估了氯通道和钾 - 氯共转运体与质子分泌之间的相互作用。这些发现突出了基因敲除动物模型在研究肾脏酸碱平衡调节中的重要性。
