The salt concentration in the renal medulla interstitial fluid is high and it varies with operation of the renal concentrating mechanism. Adaptation of cells to hypertonicity involves changes in gene expression. The kidney synthesises creatine and it also reabsorbs the filtered creatine via Na⁺/Cl^-/creatine transporter (CRT). Creatine synthesis is catalyzed by the L-Arginine:glycine amidinotransferase (AGAT) and by the guanidinoacetate methyltransferase (GAMT). We investigated whether creatine metabolism is involved in renal cell adaptation to changes in interstitial osmolarity. We achieved this by measuring the CRT, AGAT and GAMT mRNA levels, using real-time PCR, in the renal cortex and medulla of Wistar rats in two hydration states, namely, after 2,5 days of either antidiuresis or induction to drink water abundantly by adding sucrose to their drinking water. The mRNA levels of the toniciy sensitive genes coding for AQP2 (aquoporin2), BGT1 (betaine transporter) and SGK (glucocorticoid-inducible kinase) were determined for the sake of comparison. All procedures accord with current national/local ethical guidelines.

The results revealed that as compared with well hydrated animals, water deprivation increased cortical and medullar expression of BEGT1 and AQP2, and cortical expression of SGK. Cortical expression of CRT and cortical and medullar expression of AGAT were down regulated. Cortical and medullar expression of GAMT, and medullar expression of CRT and SGK were not affected by the water status. Water restriction also decreases cortical and medullar Na⁺/Cl^-/creatine transport activity. In conclusion, the kidney does not use creatine as osmotically active organic solute.

Supported by the Spanish MCyT-FEDER BFI 2003-00222