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Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Schicho, R; Bashashati, M; Bawa, M; McHugh, D; Saur, D; Hu, HM; Zimmer, A; Lutz, B; Mackie, K; Bradshaw, HB; McCafferty, DM; Sharkey, KA; Storr, M.
The atypical cannabinoid O-1602 protects against experimental colitis and inhibits neutrophil recruitment.
Inflamm Bowel Dis. 2011; 17(8):1651-1664
Doi: 10.1002/ibd.21538
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Schicho Rudolf
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- Abstract:
- Background: Cannabinoids are known to reduce intestinal inflammation. Atypical cannabinoids produce pharmacological effects via unidentified targets. We were interested in whether the atypical cannabinoid O-1602, reportedly an agonist of the putative cannabinoid receptor GPR55, reduces disease severity of dextran sulfate sodium (DSS) and trinitrobenzene sulfonic acid (TNBS)-induced colitis in C57BL/6N and CD1 mice. Methods: DSS (2.5% and 4%) was supplied in drinking water for 1 week while TNBS (4 mg) was applied as a single intrarectal bolus. Results: Both treatments caused severe colitis. Injection of O-1602 (5 mg/kg intraperitoneally) significantly reduced macroscopic and histological colitis scores, and myeloperoxidase activity. The protective effect was still present in cannabinoid receptor 1 (CB(1)) and 2 (CB(2)) double knockout mice and mice lacking the GPR55 gene. To investigate a potential mechanism underlying the protection by O-1602 we performed neutrophil chemotactic assays. O-1602 concentration-dependently inhibited migration of murine neutrophils to keratinocyte-derived chemokine (KC), N-formyl-methionyl-leucyl-phenylalanine (fMLP), and the N-formyl-peptide receptor ligand WKYMVm. The inhibitory effect of O-1602 was preserved in neutrophils from CB(1)/CB(2) double knockout and GPR55 knockout mice. No differences were seen in locomotor activity between O-1602-treated and control mice, indicating lack of central sedation by this compound. Conclusions: Our data demonstrate that O-1602 is protective against experimentally induced colitis and inhibits neutrophil recruitment independently of CB(1), CB(2), and GPR55 receptors. Thus, atypical cannabinoids represent a novel class of therapeutics that may be useful for the treatment of inflammatory bowel diseases.
- Find related publications in this database (using NLM MeSH Indexing)
- Analysis of Variance -
- Animals -
- Cannabinoids - immunology
- Chemotaxis, Leukocyte - drug effects
- Colitis - chemically induced
- Colon - drug effects
- Cyclohexanes - immunology
- Dextran Sulfate -
- Disease Models, Animal -
- Male -
- Mice -
- Mice, Inbred C57BL -
- Mice, Knockout -
- Motor Activity - drug effects
- Neutrophil Infiltration - drug effects
- Neutrophils - drug effects
- Peroxidase - metabolism
- Receptor, Cannabinoid, CB1 - genetics
- Receptor, Cannabinoid, CB2 - genetics
- Receptors, G-Protein-Coupled - agonists
- Resorcinols - immunology
- Trinitrobenzenesulfonic Acid -
- Find related publications in this database (Keywords)
- atypical cannabinoids
- colitis
- inflammatory bowel disease