Organic cation transport and cationic drug interactions in freshly isolated proximal tubular cells of the rat.
Freshly isolated proximal tubular cells (PTC) of the rat are used to study the uptake of a prototypical organic cation, tetraethylammonium (TEA), and the influence of other cationic drugs on TEA uptake. The time dependency of 50 microM TEA uptake was determined by incubating PTC for time periods from 10 sec until 60 min. TEA uptake was linear for at least 2 min and reached equilibrium after 30 min. The cell to medium ratio reached a value of 8 after 60 min, indicating marked accumulation of TEA. TEA uptake was concentration dependent and saturable, with an apparent Km of 63 +/- 7 microM and Vmax of 0.57 +/- 0.02 nmol/mg protein.min. In comparison with cells cultured on filters, the overall transport characteristics of TEA in PTC seem to resemble basolateral to apical flux. The concentration-dependent inhibition of some H2 antagonists and various cations on 32 microM TEA uptake was investigated, as well as the interaction with probenecid. Analysis of the log-concentration inhibition curves showed that mepiperphenidol, trimethoprim, famotidine and cimetidine had a high and low IC50 value, whereas ranitidine, nizatidine, cimetidine sulfoxide, N1-methylnicotinamide and probenecid had only a low IC50 value. The data reported here are comparable with those from other preparations, and it is possible to extrapolate to the human in vivo situation. Moreover, the isolation procedure is relatively simple and quick and the yield is high.
Boom
S P
SP
Department of Pharmacology, University of Nijmegen, The Netherlands.
Gribnau
F W
FW
Russel
F G
FG
D000818:Animals; D001692:Biological Transport; D002412:Cations / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects; D004347:Drug Interactions; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008759:Methylglycosides / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010695:Phlorhizin / Q000494:pharmacology; D011339:Probenecid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000378:metabolism*
D002412:Cations; D006635:Histamine H2 Antagonists; D008759:Methylglycosides; D004364:Pharmaceutical Preparations; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D010695:Phlorhizin; D011339:Probenecid