Distinct characteristics of transcellular transport between nicotine and tetraethylammonium in LLC-PK1 cells.
To clarify the mechanisms of the renal tubular secretion of nicotine, we studied transport of nicotine in the kidney epithelial cell line LLC-PK1. The transcellular transport of nicotine from the basolateral side to the apical side of the LLC-PK1 monolayers grown on membrane filters was much greater than that of tetraethylammonium. The basolateral-to-apical transport of nicotine was stimulated by lowering the pH of the apical side, accompanied by a decrease in the accumulation of nicotine. The accumulation of nicotine from the basolateral side was inhibited by unlabeled nicotine, cotinine, tetraethylammonium, cimetidine and quinidine. The uptake of nicotine across the apical membrane was inhibited by unlabeled nicotine and quinidine but not by tetraethylammonium or cimetidine. Pretreatment with p-chloromercuribenzene sulfonate caused a decrease in the transcellular transport of tetraethylammonium but not of nicotine. These results suggest that nicotine undergoes vectorial transport from basolateral side to the apical side of LLC-PK1 monolayers in a H+ gradient-dependent manner, corresponding to the secretion in the renal tubules. Nicotine transport in LLC-PK1 cells could be mediated by a transport system that is distinct from the transport system for tetraethylammonium.
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
K
K
Takami
H
H
Saito
M
M
Okuda
M
M
Takano
K I
KI
Inui
D002731:4-Chloromercuribenzenesulfonate / Q000494:pharmacology; D000818:Animals; D001693:Biological Transport, Active; D006863:Hydrogen-Ion Concentration; D018374:LLC-PK1 Cells; D009538:Nicotine / Q000378:metabolism*; D018722:Nicotinic Agonists / Q000378:metabolism*; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D013552:Swine; D019789:Tetraethylammonium / Q000378:metabolism*
D018722:Nicotinic Agonists; D013439:Sulfhydryl Reagents; D002731:4-Chloromercuribenzenesulfonate; D019789:Tetraethylammonium; D009538:Nicotine