title: G protein-coupled estrogen receptor and estrogen receptor ligands regulate colonic motility and visceral pain.
abstract: BACKGROUND
  Diarrhea-predominant irritable bowel syndrome (IBS-D) is a functional gastrointestinal (GI) disorder, which occurs more frequently in women than men. The aim of our study was to determine the role of activation of classical estrogen receptors (ER) and novel membrane receptor, G protein-coupled estrogen receptor (GPER) in human and mouse tissue and to assess the possible cross talk between these receptors in the GI tract.
  
  
  METHODS
  Immunohistochemistry was used to determine the expression of GPER in human and mouse intestines. The effect of G-1, a GPER selective agonist, and estradiol, a non-selective ER agonist, on muscle contractility was characterized in isolated preparations of the human and mouse colon. To characterize the effect of G-1 and estradiol in vivo, colonic bead expulsion test was performed. G-1 and estradiol activity on the visceral pain signaling was assessed in the mustard oil-induced abdominal pain model.
  
  
  RESULTS
  GPER is expressed in the human colon and in the mouse colon and ileum. G-1 and estradiol inhibited muscle contractility in vitro in human and mouse colon. G-1 or estradiol administered intravenously at the dose of 20 mg/kg significantly prolonged the time to bead expulsion in females. Moreover, G-1 prolonged the time to bead expulsion and inhibited GI hypermotility in both genders. The injection of G-1 or estradiol resulted in a significant reduction in the number of pain-induced behaviors in mice.
  
  
  CONCLUSIONS
  GPER and ER receptors are involved in the regulation of GI motility and visceral pain. Both may thus constitute an important pharmacological target in the IBS-D therapy.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Zielińska
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Fichna
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Texas Tech University Health Sciences Center/Paul L. Foster School of Medicine, El Paso, TX, USA.|Hotchkiss Brain Institute and Snyder Institute for Chronic Diseases, Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Bashashati
authors.affiliation: Hotchkiss Brain Institute and Snyder Institute for Chronic Diseases, Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Habibi
authors.affiliation: Division of Gastroenterology, Department of Medicine, Ludwig Maximilians University of Munich, Munich, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Sibaev
authors.affiliation: Department of Veterinary Sciences, Laboratory of Cell Biology and Histology, University of Antwerp, Antwerp, Belgium.
authors.forename: J-P
authors.initials: JP
authors.lastname: Timmermans
authors.affiliation: Hotchkiss Brain Institute and Snyder Institute for Chronic Diseases, Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.|Division of Gastroenterology, Department of Medicine, Ludwig Maximilians University of Munich, Munich, Germany.|Walter Brendel Center of Experimental Medicine, University of Munich, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Storr
mesh_terms: D000818:Animals; D003106:Colon / Q000187:drug effects / Q000502:physiology*; D003517:Cyclopentanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008024:Ligands; D008297:Male; D051379:Mice; D009924:Organ Culture Techniques; D011804:Quinolines / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000502:physiology*; D059265:Visceral Pain / Q000503:physiopathology*
chemical_list: C517943:1-(4-(6-bromobenzo(1,3)dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinolin-8-yl)ethanone; D003517:Cyclopentanes; C109584:GPER1 protein, human; D008024:Ligands; D011804:Quinolines; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D004958:Estradiol
keywords: 
  GPER
  ; G-1; abdominal pain; estradiol; hypermotility; irritable bowel syndrome