D-Serine is reabsorbed in rat renal pars recta
Silbernagl, S.; Völker, K.; Dantzler, W.H.
American Journal of Physiology 276(6): F857-F863
1999
ISSN/ISBN: 0002-9513 PMID: 10362774 Document Number: 508883
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 events are localized in the straight part of the proximal tubule. We therefore investigated if and how D-serine is reabsorbed there. We microinfused 14C-labeled D- or - L-serine + serine was 86% (EP), 90% (LP), and ~0 (ED, LLH). FR of D-serine could be saturated and inhibited 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 uptake carrier has a very low stereospecificity and is, therefore, different from that in the proximal convolution. The colocalization of exclusive reabsorption and metabolism makes the pars recta the tubule site for the recycling of the carbon structure of D-amino acids and, at the same time, the target of D-serine nephrotoxicity. Reprinted by permission of the publisher.