Uptake of Cardiovascular Drugs Into the Human Heart Expression, Regulation, and Function of the Carnitine Transporter OCTN2 (SLC22A5)

Background— To date, the uptake of drugs into the human heart by transport proteins is poorly understood. A candidate protein is the organic cation transporter novel type 2 (OCTN2) (SLC22A5), physiologically acting as a sodium-dependent transport protein for carnitine. We investigated expression and localization of OCTN2 in the human heart, uptake of drugs by OCTN2, and functional coupling of OCTN2 with the eliminating ATP-binding cassette (ABC) transporter ABCB1 (P-glycoprotein). Methods and Results— Messenger RNA levels of OCTN2 and ABCB1 were analyzed in heart samples by quantitative polymerase chain reaction. OCTN2 was expressed in all auricular samples that showed a pronounced interindividual variability (35 to 1352 copies per 20 ng of RNA). Although a single-nucleotide polymorphism in OCTN2 (G/C at position −207 of the promoter) had no influence on expression, administration of β-blockers resulted in significantly increased expression. Localization of OCTN2 by in situ hybridization, laser microdisse...