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http://purl.uniprot.org/citations/21744421http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21744421http://www.w3.org/2000/01/rdf-schema#comment"

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 (CB₁) and 2 (CB₂) 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 CB₁/CB₂ 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 CB₁, CB₂, and GPR55 receptors. Thus, atypical cannabinoids represent a novel class of therapeutics that may be useful for the treatment of inflammatory bowel diseases."xsd:string
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http://purl.uniprot.org/citations/21744421http://purl.uniprot.org/core/author"Zimmer A."xsd:string
http://purl.uniprot.org/citations/21744421http://purl.uniprot.org/core/author"Mackie K."xsd:string
http://purl.uniprot.org/citations/21744421http://purl.uniprot.org/core/author"Lutz B."xsd:string
http://purl.uniprot.org/citations/21744421http://purl.uniprot.org/core/author"Hu H.M."xsd:string
http://purl.uniprot.org/citations/21744421http://purl.uniprot.org/core/author"Bradshaw H.B."xsd:string
http://purl.uniprot.org/citations/21744421http://purl.uniprot.org/core/author"Sharkey K.A."xsd:string
http://purl.uniprot.org/citations/21744421http://purl.uniprot.org/core/author"McHugh D."xsd:string
http://purl.uniprot.org/citations/21744421http://purl.uniprot.org/core/author"McCafferty D.M."xsd:string
http://purl.uniprot.org/citations/21744421http://purl.uniprot.org/core/author"Storr M."xsd:string
http://purl.uniprot.org/citations/21744421http://purl.uniprot.org/core/author"Saur D."xsd:string
http://purl.uniprot.org/citations/21744421http://purl.uniprot.org/core/author"Bashashati M."xsd:string
http://purl.uniprot.org/citations/21744421http://purl.uniprot.org/core/author"Schicho R."xsd:string
http://purl.uniprot.org/citations/21744421http://purl.uniprot.org/core/author"Bawa M."xsd:string
http://purl.uniprot.org/citations/21744421http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/21744421http://purl.uniprot.org/core/name"Inflamm Bowel Dis"xsd:string
http://purl.uniprot.org/citations/21744421http://purl.uniprot.org/core/pages"1651-1664"xsd:string
http://purl.uniprot.org/citations/21744421http://purl.uniprot.org/core/title"The atypical cannabinoid O-1602 protects against experimental colitis and inhibits neutrophil recruitment."xsd:string
http://purl.uniprot.org/citations/21744421http://purl.uniprot.org/core/volume"17"xsd:string
http://purl.uniprot.org/citations/21744421http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/21744421
http://purl.uniprot.org/citations/21744421http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/21744421
http://purl.uniprot.org/uniprot/#_A0A385KNU8-mappedCitation-21744421http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21744421
http://purl.uniprot.org/uniprot/#_Q14BV9-mappedCitation-21744421http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21744421
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