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PMID:20547965

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Citation

Kobayashi, Y, Umemoto, T, Ohbayashi, M, Kohyama, N, Sanada, Y and Yamamoto, T (2010) Activation of cyclosporin A transport by a novel lambda light chain of human Ig surface antigen-related gene in Xenopus laevis oocytes. Drug Metab. Dispos. 38:1427-35

Abstract

In the present study, we isolated and determined the pharmacological characteristics of a novel gene encoding the lambda light chain of human Ig surface antigen-related gene (IgLC-rG). The isolated cDNA consisted of 693 base pairs that encoded a 232-amino acid protein. Northern blot analysis revealed that the IgLC-rG mRNA is expressed in the adult spleen and small intestine but not in fetal tissues. When expressed in Xenopus laevis oocytes, IgLC-rG mediated the high-affinity transport of [(3)H]cyclosporin A (CsA) (K(m) = 189.7 +/- 123.5 nM) in a sodium-dependent manner; however, other organic solutes such as p-aminohippuric acid and TEA were not transported via IgLC-rG. The transport of [(3)H]CsA by IgLC-rG was sensitive to pH. The uptake of [(3)H]CsA was trans-stimulated by CsA and GSH. Immunohistochemical analysis revealed that the IgLC-rG protein is localized at the brush border membrane in the human small intestine. Although the isolated IgLC-rG gene is a member of the human Ig lambda light chain surface antigen superfamily, our findings suggest that IgLC-rG functions as a novel transport peptide responsible for CsA in the human body. Our results should provide insight into the novel function of membrane-bound proteins, such as Igs.

Links

PubMed Online version:10.1124/dmd.109.030916

Keywords

Amino Acid Sequence; Animals; Antigens, Surface/genetics; Antigens, Surface/immunology; Antigens, Surface/metabolism; Base Sequence; Cyclosporine/metabolism; DNA, Complementary; Expressed Sequence Tags; Humans; Immunoglobulin lambda-Chains/immunology; Immunoglobulin lambda-Chains/metabolism; Immunohistochemistry; Kinetics; Molecular Sequence Data; Xenopus laevis

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:C6KXN3

GO:0006855: drug transmembrane transport

IDA: Inferred from Direct Assay:

P

Figure 3 shows that IgLC-rG had a selectivity for cyclosporin A transport

complete
CACAO 6609


HUMAN:C6KXN3

GO:0006855: drug transmembrane transport

IDA: Inferred from Direct Assay:

P

Seeded From UniProt

complete



See also

References

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