Accumulation of salicylic acid and indomethacin in isolated proximal tubular cells of the rat kidney.
The handling and accumulation of salicylic acid (SA) and indomethacin was examined in freshly isolated proximal tubular (PT) cells of the rat kidney in order to determine whether these cells provide a useful tool for studying accumulation of nonsteroidal anti-inflammatory drugs. A PT cell suspension was prepared by collagenase digestion, followed by filtration and isopycnic centrifugation. SA uptake was concentration-dependent and could be inhibited by probenecid. SA accumulated in the PT cells, and therefore, uptake is probably an active process. In the presence of probenecid, no SA accumulation was observed. Indomethacin uptake increased with time up to 2 min. Thereafter, a sharp decrease occurred, probably caused by inhibition of the oxidative phosphorylation. In the presence of probenecid, uptake was significantly reduced and no longer time-dependent. Indomethacin accumulated in the PT cells by a factor of more than 25. In the presence of probenecid, accumulation was decreased but was still considerable (approximately 10), probably as a result of binding to cellular protein. We conclude that as a result of carrier-mediated transport which is probenecid-sensitive, SA and indomethacin accumulate in the PT cells. The observed accumulation values are in accordance with previously observed values in the isolated perfused rat kidney. Therefore, freshly isolated PT cells appear to be a simple and useful model for studying the accumulation process of drugs like SA and indomethacin.
Cox
P G
PG
Department of Pharmacology, University of Nijmegen, The Netherlands.
van Os
C H
CH
Russel
F G
FG
D000818:Animals; D002478:Cells, Cultured; D007213:Indomethacin / Q000493:pharmacokinetics*; D007424:Intracellular Fluid / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008757:Methylglucosides / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012459:Salicylates / Q000493:pharmacokinetics*; D020156:Salicylic Acid
D008757:Methylglucosides; D012459:Salicylates; C027020:methylglucoside; D020156:Salicylic Acid; D007213:Indomethacin