Nakanishi T, Turner R J, Burg M B
Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung and Blood Intitute, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1989 Aug;86(15):6002-6. doi: 10.1073/pnas.86.15.6002.
Renal medullary cells contain high concentrations of myo-inositol, sorbitol, betaine, and glycerophosphocholine, whose levels vary with urinary osmolality. Accumulation of these "compatible" organic osmolytes is believed to help the cells osmoregulate in response to the high extracellular osmolality that occurs as part of the urinary concentrating mechanism. MDCK cells (a line from dog kidney) were previously shown to accumulate myo-inositol in response to increased medium osmolality. We demonstrate here that this accumulation requires the presence of myo-inositol in the medium, implying that the myo-inositol is not synthesized by the cells but rather is transported into them from the extracellular solution. The MDCK cells contain sodium-dependent myo-inositol transporters. Relative to isotonic controls, sodium-dependent myo-inositol uptake is higher in cells exposed to increased osmolality either acutely (1-7 days) or chronically (greater than 1 year). Transport is further enhanced when the cells are cultured in myo-inositol-free medium. The transport has both high- and low-affinity components. The observed changes in transport involve changes in maximal velocity of the high-affinity component but not in its Km. We conclude that renal cells can osmoregulate by changing the number (or, less likely, the transport turnover rate) of functioning sodium-dependent myo-inositol transporters.
肾髓质细胞含有高浓度的肌醇、山梨醇、甜菜碱和甘油磷酸胆碱，其水平随尿渗透压而变化。这些“相容性”有机渗透溶质的积累被认为有助于细胞在作为尿液浓缩机制一部分而出现的高细胞外渗透压下进行渗透调节。MDCK细胞（一种源自犬肾的细胞系）先前已被证明会因培养基渗透压升高而积累肌醇。我们在此证明，这种积累需要培养基中存在肌醇，这意味着肌醇不是由细胞合成的，而是从细胞外溶液转运到细胞内的。MDCK细胞含有钠依赖性肌醇转运体。相对于等渗对照，急性（1 - 7天）或慢性（超过1年）暴露于渗透压升高环境中的细胞，其钠依赖性肌醇摄取更高。当细胞在无肌醇培养基中培养时，转运进一步增强。转运具有高亲和力和低亲和力成分。观察到的转运变化涉及高亲和力成分最大速度的变化，而不是其米氏常数（Km）的变化。我们得出结论，肾细胞可以通过改变功能性钠依赖性肌醇转运体的数量（或者，可能性较小的是转运周转率）来进行渗透调节。
