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Organic cation/carnitine transporter OCTN2 (Slc22a5) is responsible for carnitine transport across apical membranes of small intestinal epithelial cells in mouse.
Mol Pharmacol. 2006 Sep; 70(3):829-37.MP

Abstract

The organic cation/carnitine transporter OCTN2 is responsible for renal tubular reabsorption of its endogenous substrate, carnitine, although its physiological role in small intestine remains controversial. Here we present direct evidence for a predominant role of OCTN2 in small intestinal absorption of carnitine based on experiments with juvenile visceral steatosis (jvs) mice, which have a hereditary deficiency of the octn2 gene. Uptake of carnitine, assessed with an Ussing-type chamber system, from the apical surface of the small intestine was saturable and higher than that from the basal surface in wild-type mice, whereas carnitine uptake having these characteristics was almost absent in jvs mice. Saturable uptake of carnitine was also confirmed in isolated enterocytes obtained from wild-type mice, and the Km value obtained (approximately 20 microM) was close to that reported for carnitine uptake by human embryonic kidney 293 cells stably expressing mouse OCTN2 (Slc22a5). The carnitine uptake by enterocytes was decreased in the presence of various types of organic cations, and this inhibition profile was similar to that of mouse OCTN2, whereas uptake of carnitine was quite small and unsaturable in enterocytes obtained from jvs mice. Immunohistochemical and immunoprecipitation analyses suggested colocalization of OCTN2 with PDZK1, an adaptor protein that functionally regulates OCTN2. Immunoelectron microscopy visualized both OCTN2 and PDZK1 in microvilli of absorptive epithelial cells. These findings indicate that OCTN2 is predominantly responsible for the uptake of carnitine from the apical surface of mouse small intestinal epithelial cells, and it may therefore be a promising target for oral delivery of therapeutic agents that are OCTN2 substrates.

Authors+Show Affiliations

Division of Pharmaceutical Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma, Kanazawa 920-1192, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16754783

Citation

Kato, Yukio, et al. "Organic Cation/carnitine Transporter OCTN2 (Slc22a5) Is Responsible for Carnitine Transport Across Apical Membranes of Small Intestinal Epithelial Cells in Mouse." Molecular Pharmacology, vol. 70, no. 3, 2006, pp. 829-37.
Kato Y, Sugiura M, Sugiura T, et al. Organic cation/carnitine transporter OCTN2 (Slc22a5) is responsible for carnitine transport across apical membranes of small intestinal epithelial cells in mouse. Mol Pharmacol. 2006;70(3):829-37.
Kato, Y., Sugiura, M., Sugiura, T., Wakayama, T., Kubo, Y., Kobayashi, D., Sai, Y., Tamai, I., Iseki, S., & Tsuji, A. (2006). Organic cation/carnitine transporter OCTN2 (Slc22a5) is responsible for carnitine transport across apical membranes of small intestinal epithelial cells in mouse. Molecular Pharmacology, 70(3), 829-37.
Kato Y, et al. Organic Cation/carnitine Transporter OCTN2 (Slc22a5) Is Responsible for Carnitine Transport Across Apical Membranes of Small Intestinal Epithelial Cells in Mouse. Mol Pharmacol. 2006;70(3):829-37. PubMed PMID: 16754783.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Organic cation/carnitine transporter OCTN2 (Slc22a5) is responsible for carnitine transport across apical membranes of small intestinal epithelial cells in mouse. AU - Kato,Yukio, AU - Sugiura,Mikihiro, AU - Sugiura,Tomoko, AU - Wakayama,Tomohiko, AU - Kubo,Yoshiyuki, AU - Kobayashi,Daisuke, AU - Sai,Yoshimichi, AU - Tamai,Ikumi, AU - Iseki,Shoichi, AU - Tsuji,Akira, Y1 - 2006/06/05/ PY - 2006/6/7/pubmed PY - 2006/9/29/medline PY - 2006/6/7/entrez SP - 829 EP - 37 JF - Molecular pharmacology JO - Mol Pharmacol VL - 70 IS - 3 N2 - The organic cation/carnitine transporter OCTN2 is responsible for renal tubular reabsorption of its endogenous substrate, carnitine, although its physiological role in small intestine remains controversial. Here we present direct evidence for a predominant role of OCTN2 in small intestinal absorption of carnitine based on experiments with juvenile visceral steatosis (jvs) mice, which have a hereditary deficiency of the octn2 gene. Uptake of carnitine, assessed with an Ussing-type chamber system, from the apical surface of the small intestine was saturable and higher than that from the basal surface in wild-type mice, whereas carnitine uptake having these characteristics was almost absent in jvs mice. Saturable uptake of carnitine was also confirmed in isolated enterocytes obtained from wild-type mice, and the Km value obtained (approximately 20 microM) was close to that reported for carnitine uptake by human embryonic kidney 293 cells stably expressing mouse OCTN2 (Slc22a5). The carnitine uptake by enterocytes was decreased in the presence of various types of organic cations, and this inhibition profile was similar to that of mouse OCTN2, whereas uptake of carnitine was quite small and unsaturable in enterocytes obtained from jvs mice. Immunohistochemical and immunoprecipitation analyses suggested colocalization of OCTN2 with PDZK1, an adaptor protein that functionally regulates OCTN2. Immunoelectron microscopy visualized both OCTN2 and PDZK1 in microvilli of absorptive epithelial cells. These findings indicate that OCTN2 is predominantly responsible for the uptake of carnitine from the apical surface of mouse small intestinal epithelial cells, and it may therefore be a promising target for oral delivery of therapeutic agents that are OCTN2 substrates. SN - 0026-895X UR - https://www.unboundmedicine.com/medline/citation/16754783/Organic_cation/carnitine_transporter_OCTN2__Slc22a5__is_responsible_for_carnitine_transport_across_apical_membranes_of_small_intestinal_epithelial_cells_in_mouse_ L2 - http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=16754783 DB - PRIME DP - Unbound Medicine ER -