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Acetyl-L-carnitine permeability across the blood-brain barrier and involvement of carnitine transporter OCTN2.
Biopharm Drug Dispos. 2003 Nov; 24(8):357-65.BD

Abstract

OCTN2 (SLC22A5), an organic cation/carnitine transporter, is widely distributed throughout the body, including the brain. In the present study, the involvement of OCTN2 in acetyl-L-carnitine (ALCAR) permeation across the blood-brain barrier (BBB) was examined using a microdialysis method in mouse. OCTN2 function was examined by comparison of wild-type mice with jvs mice, which express defective OCTN2 and are considered a model for primary systemic carnitine deficiency. Zero-net-flux method analysis indicated higher in vivo recovery of ALCAR and lower physiological ALCAR concentration in thalamus extracellular fluid (ECF) in jvs mice compared with wild-type mice. Externally added ALCAR showed significantly slower initial uptake across the BBB in jvs mouse. These results indicated that OCTN2 is functionally involved in ALCAR transfer across the BBB. Total radioactivity in ECF after i.v. administration of radiolabelled ALCAR remained constant for the rest of the experimental period. Accordingly, our results indicate that ALCAR is transported from blood to brain ECF by OCTN2 at least in part, and its concentration in brain ECF is regulated by other events such as protein binding and anabolic reactions in the brain, as well as by transport across the BBB.

Authors+Show Affiliations

Faculty of Pharmaceutical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14595704

Citation

Inano, Akihiro, et al. "Acetyl-L-carnitine Permeability Across the Blood-brain Barrier and Involvement of Carnitine Transporter OCTN2." Biopharmaceutics & Drug Disposition, vol. 24, no. 8, 2003, pp. 357-65.
Inano A, Sai Y, Nikaido H, et al. Acetyl-L-carnitine permeability across the blood-brain barrier and involvement of carnitine transporter OCTN2. Biopharm Drug Dispos. 2003;24(8):357-65.
Inano, A., Sai, Y., Nikaido, H., Hasimoto, N., Asano, M., Tsuji, A., & Tamai, I. (2003). Acetyl-L-carnitine permeability across the blood-brain barrier and involvement of carnitine transporter OCTN2. Biopharmaceutics & Drug Disposition, 24(8), 357-65.
Inano A, et al. Acetyl-L-carnitine Permeability Across the Blood-brain Barrier and Involvement of Carnitine Transporter OCTN2. Biopharm Drug Dispos. 2003;24(8):357-65. PubMed PMID: 14595704.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Acetyl-L-carnitine permeability across the blood-brain barrier and involvement of carnitine transporter OCTN2. AU - Inano,Akihiro, AU - Sai,Yoshimichi, AU - Nikaido,Hiroko, AU - Hasimoto,Noriyoshi, AU - Asano,Masahide, AU - Tsuji,Akira, AU - Tamai,Ikumi, PY - 2003/11/5/pubmed PY - 2004/6/29/medline PY - 2003/11/5/entrez SP - 357 EP - 65 JF - Biopharmaceutics & drug disposition JO - Biopharm Drug Dispos VL - 24 IS - 8 N2 - OCTN2 (SLC22A5), an organic cation/carnitine transporter, is widely distributed throughout the body, including the brain. In the present study, the involvement of OCTN2 in acetyl-L-carnitine (ALCAR) permeation across the blood-brain barrier (BBB) was examined using a microdialysis method in mouse. OCTN2 function was examined by comparison of wild-type mice with jvs mice, which express defective OCTN2 and are considered a model for primary systemic carnitine deficiency. Zero-net-flux method analysis indicated higher in vivo recovery of ALCAR and lower physiological ALCAR concentration in thalamus extracellular fluid (ECF) in jvs mice compared with wild-type mice. Externally added ALCAR showed significantly slower initial uptake across the BBB in jvs mouse. These results indicated that OCTN2 is functionally involved in ALCAR transfer across the BBB. Total radioactivity in ECF after i.v. administration of radiolabelled ALCAR remained constant for the rest of the experimental period. Accordingly, our results indicate that ALCAR is transported from blood to brain ECF by OCTN2 at least in part, and its concentration in brain ECF is regulated by other events such as protein binding and anabolic reactions in the brain, as well as by transport across the BBB. SN - 0142-2782 UR - https://www.unboundmedicine.com/medline/citation/14595704/Acetyl_L_carnitine_permeability_across_the_blood_brain_barrier_and_involvement_of_carnitine_transporter_OCTN2_ L2 - https://doi.org/10.1002/bdd.371 DB - PRIME DP - Unbound Medicine ER -