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Identification and functional study of an alternatively spliced variant of rat TRPV1 receptor mRNA
Author(s) -
Liang Yanbin,
Li Chen,
Guzman Victor M,
Wu Johnney,
Kim Moon,
Yamashiro Nancy,
Woodward David F
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a970-a
Subject(s) - trpv1 , receptor , chemistry , transmembrane domain , hek 293 cells , gene isoform , g protein coupled receptor , transient receptor potential channel , alternative splicing , agonist , microbiology and biotechnology , biochemistry , capsaicin , amino acid , complementary dna , biology , gene
Transient receptor potential vanilloid 1(TRPV1), or Vanilloid receptor 1(VR1), is a member of the TRP superfamily of nonselective cation channels. TRPV1 consists of a six transmembrane‐spanning domain, a pore region between S5 and S6, and the cytoplasmically oriented C‐ and N‐terminal regions. This receptor is activated by several endogenous ligands and noxious heat, acid as well as inflammatory factors, and has been proposed as a potential target for the treatment of pain and inflammation. Although numerous studies have reported the characterization of the splicing variants of rat, mouse and human TPRV1, these mRNA variants encoded N‐terminal deletion forms of TRPV1 receptors that are inactiveisoforms of TRPV1 receptors. Here, we report the identification and molecular cloning of a C‐terminal truncated form of rat TRPV1 receptor isolated from rat stomach and small intestines cDNA libraries. The deduced protein is designated as TRPV1c and contains 760 amino acids. When TRPV1c was expressed in HEK 293 cells, the TRPV1c acted as a ligand‐gated, Ca2+ permeable channel with similar agonist and antagonist pharmacology to wild type rat TRPV1 in FLIPR‐based Ca2+ assays. The ligands‐ stimulated TRPV1c activation was also shown to be dependent on the assay pH. Higher (pH 9) or lower (pH 5.5) assay pH will dramatically reduce ligands‐stimulated TRPV1c activity.