Decreased secretory transport of a quarternary ammonium, TBuMA, across LLC-PK1 cells by the anionic kidney extract

The effect of organic anionic (OA) fractions of various rat organ tissues on the apparent partition coefficients (APC) of quarternary ammoniums (QAs) between n-octanol and phosphate buffer (pH 7.4) and QAs transport across the LLC-PK1 cell monolayer was examined. The OA fraction was prepared by filtering the aqueous extract of each tissue through an ion-exchange cartridge (Bond Elut C18). In the presence of OA fractions of liver and kidney extracts, substantial increase in APC was observed for tributylmethylammonium (TBuMA, Mw 200) and berberine (Mw 335), but not for triethylmethylammonium (TEMA, Mw 116) and tetraethylammonium (TEA, Mw 130). Because only QAs with higher Mw than a threshold (i.e., > 200) are known to form lipophilic ion-pair complexes with certain organic anions (e.g., bile salts such as taurodeoxycholate), above results are consistent with the hypothesis that only larger Mw QAs form lipophilic ion-pair complexes with endogenous organic anionic components of the liver and kidney extracts. Considering the comparable effect between the liver and kidney extracts on the APC of TBuMA regardless of far less (1/5) content of bile salts in the kidney extract, OAs other than bile salts in the kidney appear to contribute to the formation of lipophilic ion-pair complexes. Most interestingly, the secretory (i.e., basolateral to apical direction) transport of TBuMA and berberine across the LLC-PK1 cell monolayer was decreased by the cis-presence of the kidney extract, while remained unchanged for the transport of TEMA and TEA. The kidney extract had no effect on the absorptive (i.e., apical to basolateral direction) transport and cellular (LLC-PK1) accumulation of all of these QAs. Regardless of underlying mechanisms, it is notable that OA components of liver and kidney extracts influence the APC and secretory transport of QAs with Mw > 200.