Merck
  • Home
  • Search Results
  • The GPR55 antagonist CID16020046 protects against intestinal inflammation.

The GPR55 antagonist CID16020046 protects against intestinal inflammation.

Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society (2015-08-01)
A Stančić, K Jandl, C Hasenöhrl, F Reichmann, G Marsche, R Schuligoi, A Heinemann, M Storr, R Schicho
ABSTRACT

G protein-coupled receptor 55 (GPR55) is a lysophospholipid receptor responsive to certain cannabinoids. The role of GPR55 in inflammatory processes of the gut is largely unknown. Using the recently characterized GPR55 inhibitor CID16020046, we determined the role of GPR55 in experimental intestinal inflammation and explored possible mechanisms of action. Colitis was induced by either 2.5% dextran sulfate sodium (DSS) supplemented in the drinking water of C57BL/6 mice or by a single intrarectal application of trinitrobenzene sulfonic acid (TNBS). Daily application of CID16020046 (20 mg/kg) significantly reduced inflammation scores and myeloperoxidase (MPO) activity. In the DSS colitis model, levels of tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β), and the expression of cyclooxygenase (Cox)-2 and signal transducer and activator of transcription 3 (STAT-3) were reduced in colon tissues while in TNBS-induced colitis, levels of Cox-2, IL-1β and IL-6 were significantly lowered. Evaluation of leukocyte recruitment by flow cytometry indicated reduced presence of lymphocytes and macrophages in the colon following GPR55 inhibition in DSS-induced colitis. In J774A.1 mouse macrophages, inhibition of GPR55 revealed reduced migration of macrophages and decreased CD11b expression, suggesting that direct effects of CID16020046 on macrophages may have contributed to the improvement of colitis. GPR55(-/-) knockout mice showed reduced inflammation scores as compared to wild type mice in the DSS model suggesting a pro-inflammatory role in intestinal inflammation. Pharmacological blockade of GPR55 reduces experimental intestinal inflammation by reducing leukocyte migration and activation, in particular that of macrophages. Therefore, CID16020046 represents a possible drug for the treatment of bowel inflammation.

MATERIALS
Product Number
Brand
Product Description

Supelco
SS Benzoic Acid, 2000 μg/mL in dichloromethane, analytical standard
Sigma-Aldrich
Glycerol, for molecular biology, ≥99.0%
Sigma-Aldrich
Hexadecyltrimethylammonium bromide, for molecular biology, ≥99%
Sigma-Aldrich
Glycerol, BioXtra, ≥99% (GC)
Sigma-Aldrich
Dimethyl sulfoxide, Hybri-Max, sterile-filtered, BioReagent, suitable for hybridoma, ≥99.7%
Sigma-Aldrich
Dimethyl sulfoxide, meets EP testing specifications, meets USP testing specifications
Sigma-Aldrich
Dimethyl sulfoxide, PCR Reagent
Sigma-Aldrich
Dimethyl sulfoxide, for molecular biology
Sigma-Aldrich
Dimethyl sulfoxide, ≥99.5% (GC), suitable for plant cell culture
Sigma-Aldrich
o-Dianisidine, peroxidase substrate
Sigma-Aldrich
Potassium phosphate dibasic solution, 1.0 M
Sigma-Aldrich
Glycerol, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for electrophoresis, ≥99% (GC)
Sigma-Aldrich
Hexadecyltrimethylammonium bromide, ≥98%
Sigma-Aldrich
Potassium phosphate dibasic, meets USP testing specifications
Sigma-Aldrich
Calcium chloride, anhydrous, BioReagent, suitable for insect cell culture, suitable for plant cell culture, ≥96.0%
Sigma-Aldrich
Picrylsulfonic acid solution, 5 % (w/v) in H2O, BioReagent, suitable for determination of primary amines
Sigma-Aldrich
Potassium phosphate dibasic, reagent grade, ≥98.0%
Sigma-Aldrich
Calcium chloride, meets USP testing specifications
Sigma-Aldrich
Benzoic acid, natural, ≥99.5%, FCC, FG
Sigma-Aldrich
Benzoic acid, ReagentPlus®, 99%
Sigma-Aldrich
Calcium chloride, AnhydroBeads, −10 mesh, ≥99.99% trace metals basis
Sigma-Aldrich
Calcium chloride, anhydrous, powder, 99.99% trace metals basis
Sigma-Aldrich
Benzoic acid, purified by sublimation, ≥99%
Sigma-Aldrich
Benzoic acid, ≥99.5%, FCC, FG
Sigma-Aldrich
Glycerol, ≥99.5%
Sigma-Aldrich
Potassium phosphate monobasic, ReagentPlus®
Sigma-Aldrich
Potassium phosphate monobasic, for molecular biology, ≥98.0%
Sigma-Aldrich
Potassium phosphate monobasic, powder, suitable for cell culture, suitable for insect cell culture, suitable for plant cell culture, ≥99.0%
Sigma-Aldrich
Dimethyl sulfoxide, anhydrous, ≥99.9%
Sigma-Aldrich
Potassium phosphate dibasic, 99.95% trace metals basis