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  • Title: Transport of cimetidine across the basolateral membrane of rabbit kidney proximal tubules: characterization of transport mechanisms.
    Author: Brändle E, Greven J.
    Journal: J Pharmacol Exp Ther; 1991 Sep; 258(3):1038-45. PubMed ID: 1832461.
    Abstract:
    The aim of the present study was to investigate the cellular uptake of the organic base cimetidine by isolated nonperfused proximal tubules of the rabbit kidney. Cellular uptake was regarded as indicating transport across the basolateral cell membrane inasmuch as the isolated tubules had no visible lumen under nonperfusing conditions. Cimetidine was accumulated in a concentrative manner in all segments of the proximal tubule. The cellular accumulation was, however, significantly higher in S2 and S3 segments than in the S1 segment. An analysis of cimetidine uptake by the S2 segment at cimetidine bath concentrations ranging from 5.10(-7) M to 10(-3) M provided evidence for the operation of a saturable and an apparently nonsaturable accumulation process. The saturable mechanism was assumed to represent a carrier-mediated active transport process. The intracellular cimetidine concentration was higher than expected from the electrochemical gradient and could be decreased by cooling the bath temperature from 37.5 degrees C to 22 degrees C. Potassium cyanide (10(-2) M) decreased the cimetidine cell/bath concentration ratio from 79.2 +/- 12.2 to 40.8 +/- 8.1. At a cimetidine bath concentration of 2 x 10(-7) M the cellular uptake of cimetidine was decreased to 40.8 +/- 6% of the control value by increasing the K+ concentration of the incubation medium from 5 mM to 35 mM. At a cimetidine concentration of 10(-3) M the uptake was decreased to 44.7 +/- 3.4% by the same experimental maneuver.(ABSTRACT TRUNCATED AT 250 WORDS)
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