A role for O-1602 and G protein-coupled receptor GPR55 in the control of colonic motility in mice
| Autor: | Martin Storr, Ken Mackie, Yong-Yu Li, Keith A. Sharkey, Kun Li, Burkhard Göke, Andreas Zimmer, Rudolf Schicho, Mohammad Bashashati, Dieter Saur, Jakub Fichna |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
CB1 cannabinoid-1 medicine.medical_treatment CBD cannabidiol Colonic Diseases Functional Pharmacology Receptor Cannabinoid CB2 chemistry.chemical_compound Mice 0302 clinical medicine Receptor Cannabinoid CB1 MAGL monoacylglycerol lipase GPR55 G protein-coupled receptor 55 Cannabinoid receptor type 2 Cannabidiol i.c.v. intracerebroventricular administration Molecular Targeted Therapy Receptors Cannabinoid GE gastric emptying FAAH fatty acid amide hydrolase Mice Knockout Neurons 0303 health sciences GI gastrointestinal i.p. intraperitoneal 3. Good health GPR119 COX-2 cyclooxygenase-2 population characteristics 030211 gastroenterology & hepatology geographic locations EFS electrical field stimulation Colon PPARα peroxisome proliferator-activated receptor-alpha KRS Krebs–Ringer solution Motility Myenteric Plexus Mice Inbred Strains Nerve Tissue Proteins Tissue Banks Biology In Vitro Techniques CB2 cannabinoid-2 Article LMMP longitudinal muscle-myenteric plexus layer 03 medical and health sciences Cellular and Molecular Neuroscience cDNA complementary DNA RT-PCR reverse transcription polymerase chain reaction parasitic diseases medicine TRPV1 transient receptor potential vanilloid 1 Animals Humans Cannabinoid Receptor Antagonists Cannabinoid 030304 developmental biology G protein-coupled receptor Gastrointestinal motility O-1602 Cannabinoids Muscle Smooth social sciences GPR55 chemistry Gene Expression Regulation Cannabinoid receptor antagonist human activities ECS endocannabinoid system |
| Zdroj: | Neuropharmacology |
| ISSN: | 1873-7064 |
| Popis: | Objective The G protein-coupled receptor 55 (GPR55) is a novel cannabinoid (CB) receptor, whose role in the gastrointestinal (GI) tract remains unknown. Here we studied the significance of GPR55 in the regulation of GI motility. Design GPR55 mRNA and protein expression were measured by RT-PCR and immunohistochemistry. The effects of the GPR55 agonist O-1602 and a selective antagonist cannabidiol (CBD) were studied in vitro and in vivo and compared to a non-selective cannabinoid receptor agonist WIN55,212-2. CB1/2−/− and GPR55−/− mice were employed to identify the receptors involved. Results GPR55 was localized on myenteric neurons in mouse and human colon. O-1602 concentration-dependently reduced evoked contractions in muscle strips from the colon (∼60%) and weakly (∼25%) from the ileum. These effects were reversed by CBD, but not by CB1 or CB2 receptor antagonists. I.p. and i.c.v. injections of O-1602 slowed whole gut transit and colonic bead expulsion; these effects were absent in GPR55−/− mice. WIN55,212-2 slowed whole gut transit effects, which were counteracted in the presence of a CB1 antagonist AM251. WIN55,212-2, but not O-1602 delayed gastric emptying and small intestinal transit. Locomotion, as a marker for central sedation, was reduced following WIN55,212-2, but not O-1602 treatment. Conclusion GPR55 is strongly expressed on myenteric neurons of the colon and it is selectively involved in the regulation of colonic motility. Since activation of GPR55 receptors is not associated with central sedation, the GPR55 receptor may serve as a future target for the treatment of colonic motility disorders. Highlights • G protein-coupled receptor 55 (GPR55) is a binding site for cannabinoids. • No conclusive information was available on function of GPR55 in the GI tract. • We found that targeting GPR55 at peripheral or central sites slows GI motility. • Slowing effect of GPR55 activation on GI motility is primarily observed in colon. • Targeting GPR55 may be a future tool for treatment of colonic motility disorders. |
| Databáze: | OpenAIRE |
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