Preclinical/Animal Transporters

Octn2 - rat

Octn2 (organic cation / carnitine transporter 2), rat

Aliases: CT1, UST2r
Gene name:  Solute carrier family 22 member 5 (SLC22A5)

Rat Octn2 (organic cation/carnitine transporter novel type 2) is a specific sodium/L-carnitine co-transporter [1]. OCTN2/Octn2 was one of the first uptake transporters cloned from rat [1, 2], human [3] and mouse [4] tissues, respectively. Expression of OCTN2/Octn2 is relatively ubiquitous [5]. In general, tissue distribution of OCTN2/Octn2 is similar in human and rats [6-12], while a few differences in function have been noted. OCTN2/Octn2-mediated organic cation transport is pH-sensitive [13, 14]. 
Human and rat OCTN2/Octn2 show overlapping but somewhat different substrate and inhibitor specificities. Transport properties of rat Octn2 and human OCTN2 expressed on the same genetic background using L-carnitine, a physiological substrate, and mildronate, the most efficiently transported drug was correlated by Szabó and coworkers [15]. The data indicated that despite overall similar substrate profiles, human OCTN2 had higher affinity for L-carnitine compared to rat Octn2. As free L-carnitine levels are close to its total plasma levels (20-60 µM) [16, 17], the in vitro data also means that both the human and rat transporters operate at or close to maximum rates to supply carnitine to tissues in vivo. A similar difference was observed in the affinity of OCTN2/Octn2 towards mildronate. 
Many pharmacologically important drugs were shown to affect L-carnitine transport by OCTN2/Octn2. The transporters from these two species showed different but overlapping inhibitor specificities as the differences in IC50 values were less than 3-fold for 13 of 15 compounds tested. 
Together with Octn1 and Mate1, Octn2 is capable of transporting oxaliplatin, an important drug used to treat colorectal cancer. Using animal models and overexpressing HEK293, PC12 and Flp‐in‐293 cell lines, a study observed that rat Mate1, Octn1 and Octn2 are involved in platinum accumulation at the dorsal root ganglion (DRG), oxaliplatin-induced cytotoxicity and neurotoxicity. Combined, these results indicate that Octn1, Octn2 and Mate1 are involved in the onset of peripheral neuropathy, an adverse effect associated with taking higher doses of oxaliplatin [18]. These data suggest that in vivo rat preclinical models may be applicable to predict human OCTN2-mediated toxicity and adverse events in the clinic, but in vitro differences between Octn2/OCTN2 transporter profiles should be taken into account.


1.    Schomig, E., et al., Molecular cloning and characterization of two novel transport proteins from rat kidney. FEBS Lett, 1998. 425(1): p. 79-86.
2.    Sekine, T., et al., Molecular cloning and characterization of high-affinity carnitine transporter from rat intestine. Biochem Biophys Res Commun, 1998. 251(2): p. 586-91.
3.    Tamai, I., et al., Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2. J Biol Chem, 1998. 273(32): p. 20378-82.
4.    Tamai, I., et al., Molecular and functional characterization of organic cation/carnitine transporter family in mice. J Biol Chem, 2000. 275(51): p. 40064-72.
5.    Wu, X., et al., cDNA sequence, transport function, and genomic organization of human OCTN2, a new member of the organic cation transporter family. Biochem Biophys Res Commun, 1998. 246(3): p. 589-95.
6.    Furuichi, Y., et al., Muscle contraction increases carnitine uptake via translocation of OCTN2. Biochem Biophys Res Commun, 2012. 418(4): p. 774-9.
7.    Inazu, M., et al., Functional expression of the organic cation/carnitine transporter 2 in rat astrocytes. J Neurochem, 2006. 97(2): p. 424-34.
8.    Koepsell, H. and H. Endou, The SLC22 drug transporter family. Pflugers Arch, 2004. 447(5): p. 666-76.
9.    Nishimura, M. and S. Naito, Tissue-specific mRNA expression profiles of human ATP-binding cassette and solute carrier transporter superfamilies. Drug Metab Pharmacokinet, 2005. 20(6): p. 452-77.
10.    Okura, T., S. Kato, and Y. Deguchi, Functional expression of organic cation/carnitine transporter 2 (OCTN2/SLC22A5) in human brain capillary endothelial cell line hCMEC/D3, a human blood-brain barrier model. Drug Metab Pharmacokinet, 2014. 29(1): p. 69-74.
11.    Sekine, T., et al., Cloning, functional characterization, and localization of a rat renal Na+-dicarboxylate transporter. Am J Physiol, 1998. 275(2 Pt 2): p. F298-305.
12.    Terada, T., et al., Expression profiles of various transporters for oligopeptides, amino acids and organic ions along the human digestive tract. Biochem Pharmacol, 2005. 70(12): p. 1756-63.
13.    Koepsell, H., Polyspecific organic cation transporters: their functions and interactions with drugs. Trends Pharmacol Sci, 2004. 25(7): p. 375-81.
14.    Ohashi, R., et al., Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther, 1999. 291(2): p. 778-84.
15.    Szabo, K., et al., Species specificity profiling of rat and human organic cation/carnitine transporter Slc22a5/SLC22A5 (Octn2/OCTN2). Drug Metab Pharmacokinet, 2016.
16.    Borum, P.R., Variation in tissue carnitine concentrations with age and sex in the rat. Biochem J, 1978. 176(3): p. 677-81.
17.    Kepka, A., et al., Plasma carnitine concentrations after chronic alcohol intoxication. Postepy Hig Med Dosw (Online), 2013. 67: p. 548-52.
18.    Fujita, S., et al., Identification of drug transporters contributing to oxaliplatin-induced peripheral neuropathy. J Neurochem, 2019. 148(3): p. 373-385.

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