Transport of cimetidine across the basolateral membrane of rabbit kidney proximal tubules: interaction with organic anions.
Since in whole animal studies and in man the renal clearance of cimetidine was prolonged by the coadministration of probenecid, the aim of the present study was to examine the interaction of the organic base cimetidine with the organic anion transport system at the basolateral membrane of isolated non-perfused rabbit proximal tubules. S2 segments of proximal tubules were incubated at 37.5 degrees C with 3H-cimetidine (2 x 10(-7) mol/l) or 3H-PAH (4 x 10(-6) mol/l, as a marker for the organic anion transport system) and 14C-inulin (marker for the extracellular space) for 25 min to achieve a steady state. Afterwards, a nonradiolabelled substance was added to the bath, and the change of the cellularly stored radioactivity was measured at 5-min intervals. Probenecid (5 x 10(-5) mol/l) decreased the cellular amount of 3H-cimetidine to 26% of the control value. At this concentration, furosemide and Na2SO4 had no effect. At a concentration of 10(-3) mol/l, these substances reduced the cellular 3H-cimetidine uptake to 33% (furosemide) and 57% (Na2SO4) of the control value. 10(-4) and 10(-3) mol/l succinate diminished the steady-state uptake of cimetidine to 77% and 53% of the control value, respectively. On the other hand, cimetidine (10(-3) mol/l) decreased the cellular uptake of 3H-PAH to 52% of the control value. N1-methylnicotinamide (5 x 10(-5) mol/l and 10(-3)mol/l) had no effect on the steady-state uptake of 3H-PAH. These results indicate that the organic base cimetidine, besides its high affinity for the cation transporter, also interacts with the organic anion transport system at the basolateral membrane of rabbit proximal tubules.
Brändle
E
E
Department of Pharmacology, RWTH, Aachen, FRG.
Greven
J
J
D000465:Algorithms; D000818:Animals; D000838:Anions; D002250:Carbon Radioisotopes; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002927:Cimetidine / Q000493:pharmacokinetics*; D005260:Female; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D011817:Rabbits; D014316:Tritium; D010130:p-Aminohippuric Acid / Q000032:analysis
D000838:Anions; D002250:Carbon Radioisotopes; D014316:Tritium; D002927:Cimetidine; D010130:p-Aminohippuric Acid