The endocannabinoid anandamide regulates the peristaltic reflex by reducing neuro-neuronal and neuro-muscular neurotransmission in ascending myenteric reflex pathways in rats |
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| Affiliation: | 1. Department of Internal Medicine II, Ludwig-Maximilians-University Munich, Munich, Germany;2. Walter Brendel Zentrum, Ludwig-Maximilians-University Munich, Munich, Germany;3. Center for Internal Medicine, Klinikum Garmisch-Partenkirchen, Garmisch-Partenkirchen, Germany;4. Department of Internal Medicine II, Technical University, Klinikum rechts der Isar, Munich, Germany;5. Abdomen-Endooffice, Munich, Germany;1. International Superconductivity Technology Center, ISTEC, Japan;2. Industrial Superconductivity Technology Research Association, iSTERA, Japan;1. Department of Pharmacology, Polish Academy of Sciences, Kraków, Poland;2. Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari, Bari, Italy;3. Department of Biosciences, Biotechnologies and Biopharmaceutics, Università degli Studi di Bari, Bari, Italy;1. Sackler Faculty of Medicine, Tel Aviv University, Israel;2. Department of Internal Medicine B, Sheba Medical Center, Ramat Gan, Israel;3. Israeli Defense Forces Medical Corps, Ramat Gan, Israel;4. The Pinchas Borenstein Talpiot Medical Leadership Program, Sheba Medical Center, Ramat Gan, Israel;5. Sheba Medical Center, Ramat Gan, Israel;6. Department of Management, Bar Ilan University, Ramat Gan, Israel |
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| Abstract: | BackgroundEndocannabinoids (EC) and the cannabinoid-1 (CB1) receptor are involved in the regulation of motility in the gastrointestinal (GI) tract. However, the underlying physiological mechanisms are not completely resolved. The purpose of this work was to study the physiological influence of the endocannabinoid anandamide, the putative endogenous CB1 active cannabinoid, and of the CB1 receptor on ascending peristaltic activity and to identify the involved neuro-neuronal, neuro-muscular and electrophysiological mechanisms.MethodsThe effects of anandamide and the CB1 receptor antagonist SR141716A were investigated on contractions of the circular smooth muscle of rat ileum and in longitudinal rat ileum segments where the ascending myenteric part of the peristaltic reflex was studied in a newly designed organ bath. Additionally intracellular recordings were performed in ileum and colon.ResultsAnandamide significantly reduced cholinergic twitch contractions of ileum smooth muscle whereas SR141716A caused an increase. Anandamide reduced the ascending peristaltic contraction by affecting neuro-neuronal and neuro-muscular neurotransmission. SR141716A showed opposite effects and all anandamide effects were antagonized by SR141716A (1 μM). Anandamide reduced excitatory junction potentials (EJP) and inhibitory junction potentials (IJP), whereas intestinal slow waves were not affected.ConclusionsCB1 receptors regulate force and timing of the intestinal peristaltic reflex and these actions involve interneurons and motor-neurons. The endogenous cannabinoid anandamide mediates these effects by activation of CB1 receptors. The endogenous cannabinoid system is permanently active, suggesting the CB1 receptor being a possible target for the treatment of motility related disorders. |
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| Keywords: | Anandamide Cannabinoid-1 receptor Peristaltic reflex Intestinal propulsion Enteric nervous system |
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