title: Characterization of cimetidine transport in LLCPK1 cells.
abstract: 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.
authors.affiliation: Faculty of Pharmacy, University of Toronto, Ontario, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Bendayan
authors.forename: B
authors.initials: B
authors.lastname: Lo
authors.forename: M
authors.initials: M
authors.lastname: Silverman
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001386:Azides / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002460:Cell Line; D002927:Cimetidine / Q000378:metabolism*; D019791:Guanidine; D006146:Guanidines / Q000494:pharmacology; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D018942:Macrolides; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D006180:Proton-Translocating ATPases / Q000378:metabolism; D011802:Quinidine / Q000494:pharmacology; D011803:Quinine / Q000494:pharmacology; D019810:Sodium Azide; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D013552:Swine; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001386:Azides; D002352:Carrier Proteins; D006146:Guanidines; D018942:Macrolides; D017923:Sodium-Hydrogen Exchangers; D013757:Tetraethylammonium Compounds; C057620:bafilomycin A; D009536:Niacinamide; D019789:Tetraethylammonium; D000584:Amiloride; D002927:Cimetidine; D019810:Sodium Azide; D011803:Quinine; D006180:Proton-Translocating ATPases; D011802:Quinidine; D019791:Guanidine; C024058:N(1)-methylnicotinamide