Premium
Expression and Function of Bile Acid Receptor TGR5 in Gastrointestinal Smooth Muscle
Author(s) -
Rajagopal Senthilkumar,
AlShboul Othman,
Mahavadi Sunila,
Kuemmerle John F,
Murthy Karnam S
Publication year - 2011
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.25.1_supplement.1069.5
Subject(s) - g protein coupled bile acid receptor , receptor , biology , bile acid , carbachol , adenylyl cyclase , endocrinology , western blot , medicine , muscle relaxation , signal transduction , chemistry , microbiology and biotechnology , biochemistry , gene
Bile acids, the main active constituents of bile, act, in addition to their role in nutrient absorption, as signaling molecules to exert genomic and non‐genomic effects via nuclear receptors and the plasma membrane G protein‐coupled receptor TGR5. TGR5 is expressed in epithelial cells and enteric neurons of the gastrointestinal tract and may mediate the effects of bile acids on motility and secretion. However, the mechanisms by which bile acids regulate smooth muscle function are not known. AIM To determine the expression of TGR5 in gastrointestinal smooth muscle and identify their signaling pathways. METHODS TGR5 expression was determined by RT‐PCR and western blot. G protein activation in response to TGR5 selective ligand, oleanolic acid (OA) was measured as increase in Gα binding to [ 35 S]GTPγS. OA‐induced increase in cAMP was measured by ELISA and muscle relaxation by scanning micrometry. RESULTS TGR5 expression was detected by RT‐PCR and western blot in rabbit gastric muscle and human intestinal muscle. OA activated Gα s , but not Gα q, Gα i1 , Gα i2, or Gα i3 . Consistent with activation of Gα s , OA increased cAMP levels. OA did not elicit contraction, but caused relaxation of carbachol‐induced muscle contraction. CONCLUSION Smooth muscle cells express membrane receptors (TGR5) for bile acids preferentially coupled to G s . The receptors mediate stimulation of adenylyl cyclase activity and muscle relaxation.