An extended substrate spectrum of the proton organic cation antiporter and relation to other cation transporters.

Most central nervous system (CNS) active drugs are organic cations, which need carrier proteins for efficient transfer through the blood-brain barrier (BBB). A genetically still unidentified proton organic cation (H/OC) antiporter is found in several tissues, including endothelial cells of the BBB. We characterized the substrate spectrum of the H/OC antiporter and the overlap in substrate spectrum with OCTN1, OCTN2 or OCT3 by screening 87 potential substrates for transport activity.

Several orphan solute carriers functionally identified as organic cation transporters: Substrates specificity compared with known cation transporters.

Organic cations comprise a significant part of medically relevant drugs and endogenous substances. Such substances need organic cation transporters for efficient transfer via cell membranes. However, the membrane transporters of most natural or synthetic organic cations are still unknown.

Atypical Substrates of the Organic Cation Transporter 1.

The human organic cation transporter 1 (OCT1) is expressed in the liver and mediates hepatocellular uptake of organic cations. However, some studies have indicated that OCT1 could transport neutral or even anionic substrates. This capability is interesting concerning protein-substrate interactions and the clinical relevance of OCT1.