Salicylate inhibits the renal transport of inorganic sulfate in rat membrane vesicle preparations.
Salicylic acid (SA) administration produces a pronounced enhancement of the renal clearance of inorganic sulfate in rats. The purpose of the present investigation was to determine if SA inhibits the renal transport of inorganic sulfate in rat kidney cortex brush border membrane (BBM) and basolateral membrane (BLM) vesicle preparations. Sodium-dependent cotransport of inorganic sulfate was examined in BBM, and the values for KM and Vmax, determined using nonlinear regression analysis, were 0.52 +/- 0.41 mM and 2.84 +/- 1.26 nmol/mg protein/10 sec, respectively (N = 7). Bicarbonate-dependent sulfate anion exchange was examined in BLM, and the values for KM and Vmax were 0.31 +/- 0.14 mM and 0.83 +/- 0.27 nmol/mg protein/10 sec, respectively (N = 5). SA inhibited sulfate transport into both BBM and BLM preparations. The Ki values, fitted using both competitive and noncompetitive inhibition models, were 19.4 +/- 9.2 and 26.3 +/- 12.2 mM (N = 3), respectively, for sodium/sulfate cotransport in BBM vesicles and 1.10 +/- 0.32 and 1.93 +/- 0.38 mM (N = 3), respectively, for bicarbonate-driven sulfate transport in BLM vesicles. Because SA did not transstimulate sulfate transport into vesicle preparations, this might suggest a noncompetitive inhibition mechanism. The inhibitory effect of SA appears to occur predominantly at the BLM membrane, due to the lower Ki observed in the transport studies. Therefore, the results demonstrate that SA predominantly inhibits the transport of inorganic sulfate across the renal BLM; this interaction may be responsible, at least in part, for the SA-induced increase in sulfate renal clearance that has been observed in vivo.
Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, Amherst 14260.
I M
IM
Darling
M L
ML
Mammarella
Q
Q
Chen
M E
ME
Morris
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D007474:Ion Exchange; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D012459:Salicylates / Q000494:pharmacology*; D020156:Salicylic Acid; D013431:Sulfates / Q000493:pharmacokinetics*; D013885:Thiosulfates / Q000494:pharmacology
D012459:Salicylates; D013431:Sulfates; D013885:Thiosulfates; D020156:Salicylic Acid