TISSUE DISTRIBUTION AND FUNCTIONAL CHARACTERIZATION OF ORGANIC CATION/CARNITINE TRANSPORTER OCTN1

In the present study, we examined the tissue distribution and functional characteristics of a member of organic cation/carnitine transporter family, OCTN1 in human by using membrane vesicles prepared from the HEK293 cells that were stably expressing human OCTN1. Immunohistochemical analysis of mouse OCTN1 in kidney demonstrated that OCTN1 is expressed strongly in epithelial cells of tubular cells in cortex. In epithelial cells, OCTN1 showed differential expression from Na+/K+-ATPase, which is a basolaterally localized enzyme, and exclusively expressed in the apical membrane of the cells. Membrane vesicles prepared from HEK293 cells that were stably transfected with human OCTN1 showed increased uptake of tetraethylammonium (TEA) compared with that by membrane vesicles form Mock-transfected cells. Uptake of [14C]TEA was apparently pH dependent and showed overshoot uptake in the presence of outwardly-directed proton gradient. Preloading of unlabeled TEA enhanced the initial uptake of [14C]TEA. These kinds of and other studies suggested that OCTN1 may be involved in the pH dependent apical membrane transport of organic cations in kidney and it may also functional as the organic cation/organic cation antiporter. Since OCTN1 is expressed in various tissues, OCTN1 may also contribute in the distribution and/or efflux of cationic compounds in those tissues by being energized by proton or cation gradients across the cellular membranes.