Tags

Type your tag names separated by a space and hit enter

Differential effects of CB(1) neutral antagonists and inverse agonists on gastrointestinal motility in mice.
Neurogastroenterol Motil. 2010 Jul; 22(7):787-96, e223.NM

Abstract

BACKGROUND

Cannabinoid type 1 (CB(1)) receptors are involved in the regulation of gastrointestinal (GI) motility and secretion. Our aim was to characterize the roles of the CB(1) receptor on GI motility and secretion in vitro and in vivo by using different classes of CB(1) receptor antagonists.

METHODS

Immunohistochemistry was used to examine the localization of CB(1) receptor in the mouse ileum and colon. Organ bath experiments on mouse ileum and in vivo motility testing comprising upper GI transit, colonic expulsion, and whole gut transit were performed to characterize the effects of the inverse agonist/antagonist AM251 and the neutral antagonist AM4113. As a marker of secretory function we measured short circuit current in vitro using Ussing chambers and stool fluid content in vivo in mouse colon. We also assessed colonic epithelial permeability in vitro using FITC-labeled inulin.

KEY RESULTS

In vivo, the inverse agonist AM251 increased upper GI transit and whole gut transit, but it had no effect on colonic expulsion. By contrast, the neutral antagonist AM4113 increased upper GI transit, but unexpectedly reduced both colonic expulsion and whole gut transit at high, but not lower doses.

CONCLUSIONS & INFERENCES

Cannabinoid type 1 receptors regulate small intestinal and colonic motility, but not GI secretion under physiological conditions. Cannabinoid type 1 inverse agonists and CB(1) neutral antagonists have different effects on intestinal motility. The ability of the neutral antagonist not to affect whole gut transit may be important for the future development of CB(1) receptor antagonists as therapeutic agents.

Authors+Show Affiliations

Snyder Institute of Infection, Immunity & Inflammation, Division of Gastroenterology, Department of Medicine, University Calgary, Calgary, AB, Canada. mstorr@ucalgary.caNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20180825

Citation

Storr, M A., et al. "Differential Effects of CB(1) Neutral Antagonists and Inverse Agonists On Gastrointestinal Motility in Mice." Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society, vol. 22, no. 7, 2010, pp. 787-96, e223.
Storr MA, Bashashati M, Hirota C, et al. Differential effects of CB(1) neutral antagonists and inverse agonists on gastrointestinal motility in mice. Neurogastroenterol Motil. 2010;22(7):787-96, e223.
Storr, M. A., Bashashati, M., Hirota, C., Vemuri, V. K., Keenan, C. M., Duncan, M., Lutz, B., Mackie, K., Makriyannis, A., Macnaughton, W. K., & Sharkey, K. A. (2010). Differential effects of CB(1) neutral antagonists and inverse agonists on gastrointestinal motility in mice. Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society, 22(7), 787-96, e223. https://doi.org/10.1111/j.1365-2982.2010.01478.x
Storr MA, et al. Differential Effects of CB(1) Neutral Antagonists and Inverse Agonists On Gastrointestinal Motility in Mice. Neurogastroenterol Motil. 2010;22(7):787-96, e223. PubMed PMID: 20180825.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential effects of CB(1) neutral antagonists and inverse agonists on gastrointestinal motility in mice. AU - Storr,M A, AU - Bashashati,M, AU - Hirota,C, AU - Vemuri,V K, AU - Keenan,C M, AU - Duncan,M, AU - Lutz,B, AU - Mackie,K, AU - Makriyannis,A, AU - Macnaughton,W K, AU - Sharkey,K A, Y1 - 2010/02/24/ PY - 2010/2/26/entrez PY - 2010/2/26/pubmed PY - 2010/9/18/medline SP - 787-96, e223 JF - Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society JO - Neurogastroenterol Motil VL - 22 IS - 7 N2 - BACKGROUND: Cannabinoid type 1 (CB(1)) receptors are involved in the regulation of gastrointestinal (GI) motility and secretion. Our aim was to characterize the roles of the CB(1) receptor on GI motility and secretion in vitro and in vivo by using different classes of CB(1) receptor antagonists. METHODS: Immunohistochemistry was used to examine the localization of CB(1) receptor in the mouse ileum and colon. Organ bath experiments on mouse ileum and in vivo motility testing comprising upper GI transit, colonic expulsion, and whole gut transit were performed to characterize the effects of the inverse agonist/antagonist AM251 and the neutral antagonist AM4113. As a marker of secretory function we measured short circuit current in vitro using Ussing chambers and stool fluid content in vivo in mouse colon. We also assessed colonic epithelial permeability in vitro using FITC-labeled inulin. KEY RESULTS: In vivo, the inverse agonist AM251 increased upper GI transit and whole gut transit, but it had no effect on colonic expulsion. By contrast, the neutral antagonist AM4113 increased upper GI transit, but unexpectedly reduced both colonic expulsion and whole gut transit at high, but not lower doses. CONCLUSIONS & INFERENCES: Cannabinoid type 1 receptors regulate small intestinal and colonic motility, but not GI secretion under physiological conditions. Cannabinoid type 1 inverse agonists and CB(1) neutral antagonists have different effects on intestinal motility. The ability of the neutral antagonist not to affect whole gut transit may be important for the future development of CB(1) receptor antagonists as therapeutic agents. SN - 1365-2982 UR - https://www.unboundmedicine.com/medline/citation/20180825/Differential_effects_of_CB_1__neutral_antagonists_and_inverse_agonists_on_gastrointestinal_motility_in_mice_ L2 - https://doi.org/10.1111/j.1365-2982.2010.01478.x DB - PRIME DP - Unbound Medicine ER -