Effects of Citrus Fruit Juices on Organic Cation Transporter 2 Function and Expression in Vitro

Organic cation transporter 2 (OCT2) plays an important role in the renal clearance of endogenous and exogenous organic cations, including drugs and their metabolites. Citrus fruit juice interactions with the P-gp efflux transporter are well-established, but there is to date no study on the effects of citrus fruit juice on OCT2 function and expression. This paper evaluates the modulating activities of grapefruit, pummelo, orange, lime and lemon juices on porcine OCT2 (pOCT2) in LLC-PK1 cells. pOCT2-mediated transport of rhodamine-123 (R-123) across confluent LLC-PK1 cell monolayers in the apical-to-basal direction was confirmed by transport and uptake data in the presence of tetraethylammonium (TEA) and verapamil (OCT2 and P-gp inhibitors, respectively). Grapefruit juice at 10%, and pummelo and orange juices at 10 to 30%, produced R-123 transport and cellular accumulation profiles consistent with the OCT2-inhibitory effects of TEA. Cellular pOCT2 expression was up-regulated by pummelo, orange and lime juices at 5, 30 and 10%, respectively. The effect of lime juice on pOCT2 transport activity could not be verified due to its overriding influence on the paracellular transport pathway, while lemon juice at 10 to 30% did not appear to affect the function and expression of the pOCT2 transporter. Given that grapefruit, pummelo and orange share the same taxonomic classification, it may well be that common components in these citrus fruit juices are potent modulators of the function and/or expression of the OCT2 transporter.