Activation of cyclosporin A transport by a novel lambda light chain of human Ig surface antigen-related gene in Xenopus laevis oocytes.
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.
Kobayashi
Yasuna
Y
School of Pharmacy, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, Japan.
Umemoto
Takahiro
T
Ohbayashi
Masayuki
M
Kohyama
Noriko
N
Sanada
Yutaka
Y
Yamamoto
Toshinori
T
D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001483:Base Sequence; D016572:Cyclosporine / Q000378:metabolism*; D018076:DNA, Complementary; D020224:Expressed Sequence Tags; D006801:Humans; D007146:Immunoglobulin lambda-Chains / Q000276:immunology / Q000378:metabolism*; D007150:Immunohistochemistry; D007700:Kinetics; D008969:Molecular Sequence Data; D014982:Xenopus laevis
D000954:Antigens, Surface; D018076:DNA, Complementary; D007146:Immunoglobulin lambda-Chains; D016572:Cyclosporine