ALDOSE REDUCTASE AND MYOINOSITOL TRANSPORTER MESSENGER-RNA ARE INDEPENDENTLY REGULATED IN RAT RENAL MEDULLA

During antidiuresis, renal papillary cells accumulate organic osmolyte s preferentially over inorganic ions, It has been previously demonstra ted that sodium infusion increased all of these organic osmolytes exce pt myo-inositol (1), Conversely, urea infusion increased only glycerop hosphorylcholine significantly. In addition to sodium and urea, potass ium localized in tissue and urine influenced the composition of organi c osmolytes. The goal of this study was to clarify how the level of mR NA of osmoregulatory protein is regulated by the extracellular solutes and how it affects the accumulation of organic osmolytes. To clarify the relationship between intra- or extracellular solutes and the regul ation of Na/myo-inositol cotransporter and aldose reductase, mRNA of t hese osmoregulatory proteins were determined in water-deprived sodium chloride-, potassium chloride-, and urea-loaded rats. Medullary conten t of sorbitol and myo-inositol, and aldose-reductase enzymatic activit y were measured simultaneously in these animals. In water-deprived, so dium-loaded, and potassium-loaded rats, the inner medullary sorbitol c ontent increased significantly in accordance with the rise in the enzy matic activity and the level of aldose reductase mRNA, In urea-loaded rats, both the sorbitol content and the level of aldose reductase mRNA were equal to that in hydrated rats. In the outer and inner medullary tissues, the level of myo-inositol transporter mRNA was increased in all hyperosmolality protocols, including urea infusion, which correspo nded with the rise in myo-inositol content. In conclusion, potassium c hloride infusion is as effective as water deprivation and sodium chlor ide infusion in raising the level of aldose reductase and myo-inositol transporter mRNA, whereas urea influenced only myo-inositol transport er. Although aldose reductase and myo-inositol transporter are osmoreg ulatory proteins in the renal medulla, the levels of aldose reductase and sodium-dependent myo-inositol transporter mRNA are regulated indep endently.