title: Endocannabinoids as physiological regulators of colonic propulsion in mice.
abstract: OBJECTIVE
  Activation of enteric cannabinoid CB1 receptors inhibits motility in the small intestine; however, it is not known whether endogenous cannabinoids (anandamide and 2-arachidonylglycerol) play a physiologic role in regulating intestinal motility. In the present study, we investigated the possible involvement of endocannabinoids in regulating intestinal propulsion in the mouse colon in vivo.
  
  
  METHODS
  Intestinal motility was studied measuring the expulsion of a glass bead inserted into the distal colon; endocannabinoid levels were measured by isotope-dilution gas chromatography-mass spectrometry; anandamide amidohydrolase activity was measured by specific enzyme assays. CB1 receptors were localized by immunohistochemistry.
  
  
  RESULTS
  Anandamide, WIN 55,212-2, cannabinol (nonselective cannabinoid agonists), and ACEA (a selective CB1 agonist) inhibited colonic propulsion; this effect was counteracted by SR141716A, a CB1 receptor antagonist. Administered alone, SR141716A increased motility, whereas the inhibitor of anandamide cellular reuptake, VDM11, decreased motility. High amounts of 2-arachidonylglycerol and particularly anandamide were found in the colon, together with a high activity of anandamide amidohydrolase. CB1 receptor immunoreactivity was colocalized to a subpopulation of choline acetyltransferase-immunoreactive neurons and fiber bundles in the myenteric plexus.
  
  
  CONCLUSIONS
  We conclude that endocannabinoids acting on myenteric CB1 receptors tonically inhibit colonic propulsion in mice.
authors.affiliation: Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Pinto
authors.forename: Angelo A
authors.initials: AA
authors.lastname: Izzo
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Cascio
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bisogno
authors.forename: Karen
authors.initials: K
authors.lastname: Hospodar-Scott
authors.forename: David R
authors.initials: DR
authors.lastname: Brown
authors.forename: Nicola
authors.initials: N
authors.lastname: Mascolo
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.forename: Francesco
authors.initials: F
authors.lastname: Capasso
mesh_terms: D000577:Amides; D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids / Q000378:metabolism*; D003106:Colon / Q000502:physiology*; D063388:Endocannabinoids; D004983:Ethanolamines; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010169:Palmitic Acids / Q000378:metabolism; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists / Q000037:antagonists & inhibitors; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000577:Amides; D000581:Amidohydrolases; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D063388:Endocannabinoids; D004983:Ethanolamines; D010169:Palmitic Acids; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D000099252:Fatty Acid Amide Hydrolases; C462953:N-(2-methyl-3-hydroxyphenyl)-5,8,11,14-eicosatetraenamide; C005958:palmidrol