title: The endocannabinoid anandamide regulates the peristaltic reflex by reducing neuro-neuronal and neuro-muscular neurotransmission in ascending myenteric reflex pathways in rats.
abstract: BACKGROUND
  Endocannabinoids (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.
  
  
  METHODS
  The 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.
  
  
  RESULTS
  Anandamide 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.
  
  
  CONCLUSIONS
  CB1 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.
authors.affiliation: Department of Internal Medicine II, Ludwig-Maximilians-University Munich, Munich, Germany; Walter Brendel Zentrum, Ludwig-Maximilians-University Munich, Munich, Germany. Electronic address: sibaev.andrei@med.uni-muenchen.de.
authors.forename: Andrei
authors.initials: A
authors.lastname: Sibaev
authors.affiliation: Department of Internal Medicine II, Ludwig-Maximilians-University Munich, Munich, Germany; Walter Brendel Zentrum, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Birol
authors.initials: B
authors.lastname: Yuece
authors.affiliation: Center for Internal Medicine, Klinikum Garmisch-Partenkirchen, Garmisch-Partenkirchen, Germany.
authors.forename: Hans Dieter
authors.initials: HD
authors.lastname: Allescher
authors.affiliation: Department of Internal Medicine II, Technical University, Klinikum rechts der Isar, Munich, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Saur
authors.affiliation: Department of Internal Medicine II, Ludwig-Maximilians-University Munich, Munich, Germany; Walter Brendel Zentrum, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Storr
authors.affiliation: Abdomen-Endooffice, Munich, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Kurjak
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D063388:Endocannabinoids / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials; D007082:Ileum / Q000294:innervation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009197:Myenteric Plexus / Q000502:physiology*; D010528:Peristalsis / Q000187:drug effects* / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics; D012018:Reflex / Q000187:drug effects*; D000077285:Rimonabant; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D001285:Atropine; D000077285:Rimonabant; C078814:anandamide
keywords: Anandamide; Cannabinoid-1 receptor; Enteric nervous system; Intestinal propulsion; Peristaltic reflex