Endocannabinoids as physiological regulators of colonic propulsion in mice

Gastroenterology. 2002 Jul;123(1):227-34. doi: 10.1053/gast.2002.34242.


Background & aims: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amides
  • Amidohydrolases / metabolism
  • Animals
  • Arachidonic Acids / pharmacology
  • Cannabinoid Receptor Modulators
  • Cannabinoids / metabolism*
  • Colon / physiology*
  • Endocannabinoids
  • Ethanolamines
  • Gastrointestinal Motility / drug effects
  • Gastrointestinal Motility / physiology*
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Inbred ICR
  • Palmitic Acids / metabolism
  • Receptors, Cannabinoid
  • Receptors, Drug / agonists
  • Receptors, Drug / antagonists & inhibitors


  • Amides
  • Arachidonic Acids
  • Cannabinoid Receptor Modulators
  • Cannabinoids
  • Endocannabinoids
  • Ethanolamines
  • N-(2-methyl-3-hydroxyphenyl)-5,8,11,14-eicosatetraenamide
  • Palmitic Acids
  • Receptors, Cannabinoid
  • Receptors, Drug
  • palmidrol
  • Amidohydrolases
  • fatty-acid amide hydrolase