D-serine is reabsorbed in rat renal pars recta

D-Serine normally contributes up to 3% to total plasma serine and up to 23% in chronic renal failure. D-Serine is metabolized by tubular D-amino acid oxidase (D-AAO), and high D-serine plasma levels are nephrotoxic; both even ts are localized in the straight part of the proximal tubule. We therefore investigated if and how D-serine is reabsorbed there. We microinfused C-14- labeled D- or -L-serine + [H-3]inulin into early proximal (EP), late proxim al (LP), or early distal (ED) tubule sections of superficial nephrons and i nto long loops of Henle (LLH) of rats in vivo and in situ. The fractional r eabsorption (FR) of the C-14 label was determined from the C-14:H-3 ratio i n the final urine. At 0.36 mM, FR of D-[C-14]serine was 86% (EP), 90% (LP), and approximate to 0 (ED, LLH). FR of D-serine could be saturated and inhi bited by L-serine (and vice versa). D-methionine, but not D-glutamate or D- arginine, blocked FR of D-serine (LP). We conlude that filtered D-serine is able to enter the pars recta cells, thereby getting access to D-AAO. The u ptake carrier has a very low stereospecificity and is, therefore, different from that in the proximal convolution. The colocalization of exclusive rea bsorption and metabolism makes the pars recta the tubule site for the recyc ling of the carbon structure of D-amino acids and, at the same time, the ta rget of D-serine nephrotoxicity.