Abstract
In the present study, we isolated and determined the pharmacological characteristics of a novel gene encoding the λ 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 [3H]cyclosporin A (CsA) (Km = 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 [3H]CsA by IgLC-rG was sensitive to pH. The uptake of [3H]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 λ 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.
Footnotes
This work was supported in part by Grants-in-Aid for Exploratory Research [19659329]; and “High-Tech Research Center” Project for Private Universities with matching fund subsidy from the Ministry of Education, Culture, Sports, Science and Technology, 2005–2009.
Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
doi:10.1124/dmd.109.030916.
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ABBREVIATIONS:
- OAT/Oat
- organic anion transporter
- SLC/Slc
- solute carrier
- OATP/Oatp
- organic anion transporting polypeptide
- TMDs
- transmembrane domains
- ABC
- ATP-binding cassette
- 4F2hc
- 4F2 heavy chain
- CsA
- cyclosporin A
- IgLC-rG
- the λ light chain of human Ig surface antigen-related gene
- PAH
- p-aminohippuric acid
- 6-MP
- 6-mercaptopurine
- MTX
- methotrexate
- TEA
- tetraethylammonium
- DEX
- dexamethasone
- dCTP
- deoxycytidine [5′-α-32P]triphosphate
- EST
- expressed sequence tag
- EMBL
- European Molecular Biology Laboratory
- DDBJ
- DNA Data Bank of Japan
- PCR
- polymerase chain reaction
- SSC
- standard saline citrate
- MES
- 4-morpholineethanesulfonic acid
- SASP
- salazosulfapyridine, sulfasalazine
- DMSO
- dimethyl sulfoxide
- kb
- kilobase
- VC
- vitamin C
- Ost
- organic solute transporter
- PG
- prostaglandin
- FK506
- tacrolimus.
- Received December 1, 2009.
- Accepted June 14, 2010.
- Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics
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