Effect of antidiuresis on renal creatine metabolism

The current work investigates whether creatine metabolism is involved in renal adaptation to dehydration. Wistar rats were either deprived of water or induced to drink water abundantly during 60 h. Cortical and medullar mRNA levels of Na(+)/Cl(-)/creatine transporter (CRT), l-arginine: glycine amidinotransferase (AGAT), guanidinoacetate methyltransferase (GAMT) and of the tonicity sensitive genes coding for aquaporin 2, Na(+)/Cl(-)/betaine transporter and glucocorticoid-inducible kinase were measured by real-time PCR assays. The activity of the CRT and that of Na(+)/alpha-methyl-glucose transporter were evaluated in renal brush-border membrane vesicles. In water loaded animals, the mRNA levels of AGAT and CRT, and the activity of the CRT were greater in the cortex than in the medulla. GAMT mRNA levels were of similar magnitude and lower than those of AGAT mRNA. Dehydration decreased cortical and medullar AGAT and CRT mRNA levels and CRT activity and it did no affect GAMT mRNA abundance. These decreases were creatine specific because dehydration increased Na(+)/alpha-methyl-glucose transporter activity and the mRNA abundance of aquaporin 2, Na(+)/Cl(-)/betaine transporter and glucocorticoid-inducible kinase. In conclusion, this is the first report showing that: i) the kidneys express significant amounts of GAMT mRNA, ii) dehydration down-regulates the expression of AGAT gene and iii) dehydration down-regulates CRT gene expression and activity.