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Journal of the American Society of Nephrology, Vol 5, 75-84, Copyright © 1994 by American Society of Nephrology

REGULAR ARTICLES

Characterization of cimetidine transport in LLCPK1 cells

R Bendayan, B Lo and M Silverman
Faculty of Pharmacy, University of Toronto, Ontario, Canada.

In this study, cimetidine uptake and its regulation by LLCPK1 monolayers were investigated. Uptake was temperature dependent with kinetic and specificity characteristics typical of a carrier-mediated mechanism. With cimetidine uptake in the presence of an excess concentration of the potent inhibitor quinidine as a measure of nonspecific transport, the estimated kinetic parameters for cimetidine uptake at 37 degrees C under steady-state conditions are Km = 32.3 +/- 6.4 microM and Vmax = 20.2 +/- 2.1 pmol/mg per minute. Amiloride, quinidine, and quinine inhibited cimetidine uptake, whereas N1- methylnicotinamide, tetraethylammonium, and guanidine did not. The uptake of cimetidine was increased in the presence of a cell-->lumen H+ gradient, consistent with the behavior of a cimetidine-H+ antiport system. Furthermore, the activity of both the Na(+)-H+ exchanger and H(+)-ATPase acted to dissipate the cell-->lumen H+ gradient, thereby decreasing net cimetidine transport. These results suggest that there is a cimetidine-H+ exchange system in LLCPK1 cells and that the net secretion of organic base in vivo may be regulated by luminal acidification mechanisms.


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