D-penicillamine and the transport of L-cystine by rat and human renal cortical brush-border membrane vesicles.
Brush-border membrane vesicles (BBMV) were prepared from rat and human renal cortical tissue by magnesium aggregation and differential centrifugation, and the uptake of L-cystine, L-cysteine, and L-cysteine-D-penicillamine were assessed by a rapid-filtration technique. L-Cystine uptake was relatively sodium independent and associated with membrane binding. Sodium-stimulated uptake was sensitive to a cation but not anion diffusion potential. Both sodium-independent and sodium-stimulated uptake rates were inhibited by the cationic L-amino acids and by some neutral L-amino acids. The uptake rates of L-cysteine and L-cysteine-D-penicillamine were more sodium dependent, and sodium-stimulated uptake rates were more sensitive to cation and anion diffusion potentials. Neither the sodium-independent nor the sodium-stimulated uptake rates of L-cysteine or L-cysteine-D-penicillamine were inhibited by the cationic L-amino acids. L-Cysteine-D-penicillamine showed relatively little membrane binding. It is concluded that L-cystine is transported into renal cortical BBMV by pathways distinct from those concerned with the transport of L-cysteine and L-cysteine-D-penicillamine, and it is postulated that these differences may account for some of the effects of D-penicillamine in cystinuria.
Furlong
T J
TJ
Department of Medicine, Royal North Shore Hospital, St. Leonards, New South Wales, Australia.
Posen
S
S
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003553:Cystine / Q000378:metabolism*; D003958:Diamide / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007672:Kidney Cortex / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008871:Microvilli / Q000378:metabolism; D010396:Penicillamine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000494:pharmacology
D000596:Amino Acids; D003958:Diamide; D003553:Cystine; D012964:Sodium; D010396:Penicillamine; D005947:Glucose; D004229:Dithiothreitol