title: Mixed MOP/DOP agonist biphalin elicits anti-transit effect in mouse models mimicking diarrhea-predominant irritable bowel syndrome symptoms.
abstract: BACKGROUND
  Opioid receptors play a crucial role in the maintenance of homeostasis in the gastrointestinal (GI) tract. The aim of this study was to characterize the effect of biphalin, a mixed MOP/DOP agonist, on mouse intestinal contractility in vitro and GI motility in vivo and in animal models mimicking symptoms of diarrhea-predominant irritable bowel syndrome (IBS-D).
  
  
  METHODS
  The effect of biphalin on muscle contractility in vitro was characterized in the ileum and colon. The anti-transit activity of biphalin in vivo was assessed in the following tests: whole gastrointestinal transit, colonic bead expulsion, fecal pellet output and castor oil-induced diarrhea, alone and in the presence of naloxone, and MOP and DOP antagonists.
  
  
  RESULTS
  In vitro, biphalin (10(-10)-10(-6)M) inhibited colonic and ileal smooth muscle contractions in a concentration-dependent, opioid antagonist-reversible manner. In vivo, biphalin at the dose of 5mg/kg ip prolonged the whole GI transit and inhibited colonic bead expulsion. Biphalin reversed hypermotility and exerted anti-diarrheal effect in mouse models mimicking IBS-D symptoms.
  
  
  CONCLUSIONS
  Biphalin is an interesting template for novel opioid-based agents to be used in therapy of functional GI diseases.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Łódź, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Zielińska
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Łódź, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Jarmuż
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Łódź, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Sałaga
authors.affiliation: Mossakowski Medical Research Centre, Polish Academy of Sciences, Warszawa, Poland.
authors.forename: Andrzej W
authors.initials: AW
authors.lastname: Lipkowski
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Łódź, Poland; Mossakowski Medical Research Centre, Polish Academy of Sciences, Warszawa, Poland. Electronic address: jakub.fichna@umed.lodz.pl.
authors.forename: Jakub
authors.initials: J
authors.lastname: Fichna
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D003967:Diarrhea / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004745:Enkephalins / Q000494:pharmacology / Q000627:therapeutic use*; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology; D043183:Irritable Bowel Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009924:Organ Culture Techniques; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D004745:Enkephalins; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C053673:biphalin
keywords: Biphalin; Diarrhea; Irritable bowel syndrome; Mixed opioid agonists