TY - JOUR
T1 - Endocannabinoids as physiological regulators of colonic propulsion in mice
AU - Pinto, Luisa
AU - Izzo, Angelo A.
AU - Cascio, Maria Grazia
AU - Bisogno, Tiziana
AU - Hospodar-Scott, Karen
AU - Brown, David R.
AU - Mascolo, Nicola
AU - Di Marzo, Vincenzo
AU - Capasso, Francesco
N1 - Funding Information:
Supported by Cofinanziamento Murst, the Enrico and Enrica Sovena Foundation (Roma), and SESIRCA (Regione Campania) a grant from the National Institutes of Health (DA-10200 to D.R.B.), and a grant from MURST Fondi Strutturali (to V.D.M.).
PY - 2002
Y1 - 2002
N2 - 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 (non-selective 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.
AB - 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 (non-selective 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.
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U2 - 10.1053/gast.2002.34242
DO - 10.1053/gast.2002.34242
M3 - Article
C2 - 12105851
AN - SCOPUS:0036307592
SN - 0016-5085
VL - 123
SP - 227
EP - 234
JO - Gastroenterology
JF - Gastroenterology
IS - 1
ER -