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Activation of cannabinoid 2 receptor relieves colonic hypermotility in a rat model of irritable bowel syndrome.
Neurogastroenterol Motil 2019; 31(6):e13555NM

Abstract

BACKGROUND

Irritable bowel syndrome (IBS) is a common disease with intestinal dysmotility, whose mechanism remains elusive. The endocannabinoid system is emerging as an important modulator of gastrointestinal (GI) motility in multiple diseases, but its involvement in IBS is unknown. We aimed to determine whether cannabinoid 2 (CB2) receptor modulates intestinal motility associated with stress-induced IBS.

METHODS

A rat IBS model was established by chronic water avoidance stress (WAS). Colonic pathological alterations were detected histologically and intestinal motility was assessed by intestinal transit time (ITT) and fecal water content (FWC). Visceral sensitivity was determined by visceromotor response (VMR) to colorectal distension (CRD). Real-time PCR, western blot, and immunostaining were performed to identify colonic CB2 receptor expression. Colonic muscle strip contractility was studied by isometric transducers and nitric oxide (NO) was detected by the Griess test. The effects of AM1241, a selective agonist of CB2 receptors, on colonic motility were examined.

KEY RESULTS

After 10 days of WAS exposure, ITT was decreased and FWC elevated while VMR magnitude in response to CRD was significantly enhanced. Colon CB2 protein and mRNA levels increased and density of CB2-positive macrophages in the mucosa and enteric neurons in the myenteric plexus was higher than in controls. Pharmacological enhancement of CB2 activity by AM1241 relieved colonic hypermotility in WAS rats in a concentration-dependent manner via inhibition of p38 phosphorylation and elevation of NO production.

CONCLUSION

CB2 receptor may exert an important inhibitory effect in stress-induced colonic hypermotility by modulating NO synthesis through p38 mitogen-activated protein kinase signaling. AM1241 could be used as a potential drug to treat disorders with colonic hypermotility.

Authors+Show Affiliations

Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China. Key Laboratory of Hubei Province for Digestive System Diseases, Wuhan, China.Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China. Key Laboratory of Hubei Province for Digestive System Diseases, Wuhan, China.Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China. Key Laboratory of Hubei Province for Digestive System Diseases, Wuhan, China.Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China. Key Laboratory of Hubei Province for Digestive System Diseases, Wuhan, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30793435

Citation

Lin, Mengjuan, et al. "Activation of Cannabinoid 2 Receptor Relieves Colonic Hypermotility in a Rat Model of Irritable Bowel Syndrome." Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society, vol. 31, no. 6, 2019, pp. e13555.
Lin M, Chen L, Xiao Y, et al. Activation of cannabinoid 2 receptor relieves colonic hypermotility in a rat model of irritable bowel syndrome. Neurogastroenterol Motil. 2019;31(6):e13555.
Lin, M., Chen, L., Xiao, Y., & Yu, B. (2019). Activation of cannabinoid 2 receptor relieves colonic hypermotility in a rat model of irritable bowel syndrome. Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society, 31(6), pp. e13555. doi:10.1111/nmo.13555.
Lin M, et al. Activation of Cannabinoid 2 Receptor Relieves Colonic Hypermotility in a Rat Model of Irritable Bowel Syndrome. Neurogastroenterol Motil. 2019;31(6):e13555. PubMed PMID: 30793435.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of cannabinoid 2 receptor relieves colonic hypermotility in a rat model of irritable bowel syndrome. AU - Lin,Mengjuan, AU - Chen,Lei, AU - Xiao,Yong, AU - Yu,Baoping, Y1 - 2019/02/21/ PY - 2018/10/16/received PY - 2018/11/30/revised PY - 2018/12/25/accepted PY - 2019/2/23/pubmed PY - 2019/2/23/medline PY - 2019/2/23/entrez KW - cannabinoid 2 receptor KW - gastrointestinal motility KW - irritable bowel syndrome KW - macrophages KW - myenteric plexus SP - e13555 EP - e13555 JF - Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society JO - Neurogastroenterol. Motil. VL - 31 IS - 6 N2 - BACKGROUND: Irritable bowel syndrome (IBS) is a common disease with intestinal dysmotility, whose mechanism remains elusive. The endocannabinoid system is emerging as an important modulator of gastrointestinal (GI) motility in multiple diseases, but its involvement in IBS is unknown. We aimed to determine whether cannabinoid 2 (CB2) receptor modulates intestinal motility associated with stress-induced IBS. METHODS: A rat IBS model was established by chronic water avoidance stress (WAS). Colonic pathological alterations were detected histologically and intestinal motility was assessed by intestinal transit time (ITT) and fecal water content (FWC). Visceral sensitivity was determined by visceromotor response (VMR) to colorectal distension (CRD). Real-time PCR, western blot, and immunostaining were performed to identify colonic CB2 receptor expression. Colonic muscle strip contractility was studied by isometric transducers and nitric oxide (NO) was detected by the Griess test. The effects of AM1241, a selective agonist of CB2 receptors, on colonic motility were examined. KEY RESULTS: After 10 days of WAS exposure, ITT was decreased and FWC elevated while VMR magnitude in response to CRD was significantly enhanced. Colon CB2 protein and mRNA levels increased and density of CB2-positive macrophages in the mucosa and enteric neurons in the myenteric plexus was higher than in controls. Pharmacological enhancement of CB2 activity by AM1241 relieved colonic hypermotility in WAS rats in a concentration-dependent manner via inhibition of p38 phosphorylation and elevation of NO production. CONCLUSION: CB2 receptor may exert an important inhibitory effect in stress-induced colonic hypermotility by modulating NO synthesis through p38 mitogen-activated protein kinase signaling. AM1241 could be used as a potential drug to treat disorders with colonic hypermotility. SN - 1365-2982 UR - https://www.unboundmedicine.com/medline/citation/30793435/Activation_of_cannabinoid_2_receptor_relieves_colonic_hypermotility_in_a_rat_model_of_irritable_bowel_syndrome L2 - https://doi.org/10.1111/nmo.13555 DB - PRIME DP - Unbound Medicine ER -