Contribution of ion-pair complexation with bile salts to the transport of organic cations across LLC-PK1 cell monolayers.
OBJECTIVE
To examine the effect of ion-pair complexation with endogenous bile salts on the transport of organic cations (OCs) across LLC-PK1 cell monolayers.


METHODS
The transport of tributylmethyl-ammonium (TBuMA) and triethylmethylammonium (TEMA) across the cell monolayer was measured in the presence of taurodeoxycholate (TDC), an endogenous organic anion that forms an ion-pair complex with TBuMA, but not with TEMA.


RESULTS
Under proton gradient conditions (i.e., pH 6.0 apical/pH 7.4 basal), the above OCs exhibited similar transport charactersistics, consistent with the well-established OC/H+ antiporter, and the presence of TDC had no measurable effect on the transport of these OCs. Under pH-equilibrated conditions (i.e., pH 7.4 apical/pH 7.4 basal); however. basal to apical transport of TBuMA, not that of TEMA, was increased in the presence of TDC, probably as a result of the formation of a lipophilic ion-pair complex between TBuMA and TDC. The transport and efflux of the TBuMA-TDC complex across the apical membrane of the cell was inhibited by representative substrates of the P-glycoprotein (P-gp), indicating the involvement of P-gp in this process. The increased affinity of the ion-pair complex to P-gp is consistent with a mechanism involving increased transport.


CONCLUSIONS
In cases where there is no proton gradient between the plasma and urine, the formation of lipophilic ion-pair complexes in the kidney with endogenous bile salts might be involved in the in vivo urinary excretion of large Mw OCs, such as TBuMA.
Department of Pharmaceutics, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
Im-Sook
IS
Song
Yong-Hae
YH
Han
Suk-Jae
SJ
Chung
Chang-Koo
CK
Shim
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D001693:Biological Transport, Active; D002412:Cations; D018374:LLC-PK1 Cells / Q000378:metabolism*; D013552:Swine; D013657:Taurodeoxycholic Acid / Q000493:pharmacokinetics
D001647:Bile Acids and Salts; D002412:Cations; D013657:Taurodeoxycholic Acid