PT  - JOURNAL ARTICLE
AU  - Rikiya Ohashi
AU  - Ikumi Tamai
AU  - Jun-ichi Nezu
AU  - Hiroko Nikaido
AU  - Noriyoshi Hashimoto
AU  - Asuka Oku
AU  - Yoshimichi Sai
AU  - Miyuki Shimane
AU  - Akira Tsuji
TI  - Molecular and Physiological Evidence for Multifunctionality of Carnitine/Organic Cation Transporter OCTN2
AID  - 10.1124/mol.59.2.358
DP  - 2001 Feb 01
TA  - Molecular Pharmacology
PG  - 358--366
VI  - 59
IP  - 2
4099  - http://molpharm.aspetjournals.org/content/59/2/358.short
4100  - http://molpharm.aspetjournals.org/content/59/2/358.full
SO  - Mol Pharmacol2001 Feb 01; 59
AB  - OCTN2 is an Na+-dependent transporter for carnitine, which is essential for fatty acid metabolism, and its functional defect leads to fatal systemic carnitine deficiency (SCD). It also transports the organic cation tetraethylammonium (TEA) in an Na+-independent manner. Here, we studied the multifunctionality of OCTN2, by examining the transport characteristics in cells transfected with mouse OCTN2 and in juvenile visceral steatosis (jvs) mice that exhibit a SCD phenotype owing to mutation of the OCTN2 gene. The physiological significance of OCTN2 as an organic cation transporter was confirmed by usingjvs mice. The embryonic fibroblasts fromjvs mice exhibited significantly decreased transport of [14C]TEA. Pharmacokinetic analysis of [14C]TEA disposition demonstrated that jvsmice showed decreased tissue distribution and renal secretory clearance. In transport experiments using OCTN2-expressing cells, TEA and carnitine showed mutual trans-stimulation effects in their transport, implying a carnitine/TEA exchange mechanism. In addition, Na+ affected the affinity of carnitine for OCTN2, whereas Na+ is unlikely to be involved in TEA transport. This is the first molecular and physiological demonstration of the operation of an organic cation transporter in renal apical membrane. The results are consistent with the physiological coupling of carnitine reabsorption with the secretion of organic cations.