Bagnasco S M, Murphy H R, Bedford J J, Burg M B
National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892.
Am J Physiol. 1988 Jun;254(6 Pt 1):C788-92. doi: 10.1152/ajpcell.1988.254.6.C788.
Renal medullary extracellular NaCl concentration is high during antidiuresis. To compensate, the cells accumulate large amounts of nonperturbing, osmotically active solutes (organic "osmolytes"), including sorbitol. GRB-PAP1 is a continuous line of epithelial cells from rabbit inner medulla. These cells accumulate sorbitol when medium NaCl concentration is elevated. The accumulation involves increase in aldose reductase, which catalyzes production of sorbitol from glucose. The purpose of the present study was to investigate control of cell sorbitol once aldose reductase was induced. We measured cell sorbitol, cell-to-medium sorbitol flux, and aldose reductase in cells grown in medium made hyperosmotic (600 mosmol/kg) with added NaCl and at intervals after medium osmolality was reduced to 300 mosmol/kg. In the hyperosmotic medium, cell sorbitol averaged 990 mmol/kg protein (approximately 260 mM), and its flux into the medium was 740 mmol.kg cell protein-1.day-1 (permeability less than 2 X 10(-9) cm/s). Within 5 min after return to isosmotic medium, sorbitol efflux increased greater than 150-fold. By the end of 1 day, cell sorbitol fell 77% but aldose reductase decreased only 10%. Aldose reductase then fell slowly to low levels over 2 wk. Thus renal medullary cells, chronically adapted to high NaCl, reduced their sorbitol level on return to isosmotic conditions by at least two mechanisms: 1) rapid increase in sorbitol flux into the medium, and 2) slow changes in the amount of aldose reductase.
抗利尿期间肾髓质细胞外氯化钠浓度较高。作为补偿，细胞会积累大量无干扰的、具有渗透活性的溶质（有机“渗透溶质”），包括山梨醇。GRB - PAP1是源自兔肾内髓质的上皮细胞系。当培养基中氯化钠浓度升高时，这些细胞会积累山梨醇。这种积累涉及醛糖还原酶的增加，醛糖还原酶催化由葡萄糖生成山梨醇。本研究的目的是在醛糖还原酶被诱导后，研究细胞中山梨醇的调控机制。我们测量了在添加氯化钠使其渗透压升高至600 mosmol/kg的培养基中生长的细胞，以及在培养基渗透压降至300 mosmol/kg后的不同时间间隔下，细胞中的山梨醇、细胞与培养基之间的山梨醇通量以及醛糖还原酶。在高渗培养基中，细胞中山梨醇平均为990 mmol/kg蛋白质（约260 mM），其向培养基中的通量为740 mmol·kg细胞蛋白质⁻¹·天⁻¹（渗透率小于2×10⁻⁹ cm/s）。回到等渗培养基后5分钟内，山梨醇外流增加超过150倍。到第1天结束时，细胞中山梨醇下降了77%，但醛糖还原酶仅下降了10%。然后醛糖还原酶在2周内缓慢降至低水平。因此，长期适应高氯化钠环境的肾髓质细胞，在回到等渗条件时，通过至少两种机制降低其山梨醇水平：1）山梨醇向培养基中的通量迅速增加，2）醛糖还原酶量的缓慢变化。
