Anti-inflammatory and antinociceptive effects of the selective cannabinoid CB2 receptor agonist ABK5
Cannabinoid receptors are a potential target for anti-inflammatory and pain therapeutics. There are two subtypes, CB1 and CB2, and Δ9-tetrahydrocannabinol activates both of them, providing an analgesic effect but also psychoactive side effects. The psychoactive side effects are considered to be caus...
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doaj-ac06208db58d40e38807b7cf24277a362021-03-11T04:24:08ZengElsevierJournal of Pharmacological Sciences1347-86132021-04-011454319326Anti-inflammatory and antinociceptive effects of the selective cannabinoid CB2 receptor agonist ABK5Yaliang Tang0Barbara Wolk1Stevie C. Britch2Rebecca M. Craft3Debra A. Kendall4Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, 06269, USADepartment of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, 06269, USADepartment of Psychology, Washington State University, Pullman, WA, 99164, USADepartment of Psychology, Washington State University, Pullman, WA, 99164, USADepartment of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, 06269, USA; Corresponding author. Department of Pharmaceutical Sciences, University of Connecticut, 69 N. Eagleville Road, Storrs, CT, 06269-3092, USA.Cannabinoid receptors are a potential target for anti-inflammatory and pain therapeutics. There are two subtypes, CB1 and CB2, and Δ9-tetrahydrocannabinol activates both of them, providing an analgesic effect but also psychoactive side effects. The psychoactive side effects are considered to be caused by activation of CB1, but not CB2. ABK5 is a CB2 subtype selective agonist that has a very different structure from known cannabinoid receptor agonists. Here, we report anti-inflammatory effects of ABK5 using the T-cell line Jurkat cells, and antinociceptive effect in an inflammatory pain model in rats. Production of the cytokines IL-2 and TNF-α was measured in stimulated Jurkat cells and MOLT-4 cells, and CXCL12-mediated chemotaxis of Jurkat cells was evaluated by a transwell migration assay. Anti-inflammatory and antinociceptive effects of ABK5 were also evaluated in a hindpaw CFA model in rats. ABK5 significantly decreased production of IL-2 and TNF-α measured as both mRNA and protein levels, and reduced chemotaxis towards CXCL12. It also attenuated edema and increased mechanical threshold in the hindpaw of CFA-treated rats. These results suggest that ABK5 is a good lead compound for the development of potential anti-inflammatory and analgesic agents.http://www.sciencedirect.com/science/article/pii/S1347861320301250Cannabinoid receptor CB2 agonistPro-inflammatory cytokinesCell migrationAnti-inflammationInflammatory pain |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yaliang Tang Barbara Wolk Stevie C. Britch Rebecca M. Craft Debra A. Kendall |
spellingShingle |
Yaliang Tang Barbara Wolk Stevie C. Britch Rebecca M. Craft Debra A. Kendall Anti-inflammatory and antinociceptive effects of the selective cannabinoid CB2 receptor agonist ABK5 Journal of Pharmacological Sciences Cannabinoid receptor CB2 agonist Pro-inflammatory cytokines Cell migration Anti-inflammation Inflammatory pain |
author_facet |
Yaliang Tang Barbara Wolk Stevie C. Britch Rebecca M. Craft Debra A. Kendall |
author_sort |
Yaliang Tang |
title |
Anti-inflammatory and antinociceptive effects of the selective cannabinoid CB2 receptor agonist ABK5 |
title_short |
Anti-inflammatory and antinociceptive effects of the selective cannabinoid CB2 receptor agonist ABK5 |
title_full |
Anti-inflammatory and antinociceptive effects of the selective cannabinoid CB2 receptor agonist ABK5 |
title_fullStr |
Anti-inflammatory and antinociceptive effects of the selective cannabinoid CB2 receptor agonist ABK5 |
title_full_unstemmed |
Anti-inflammatory and antinociceptive effects of the selective cannabinoid CB2 receptor agonist ABK5 |
title_sort |
anti-inflammatory and antinociceptive effects of the selective cannabinoid cb2 receptor agonist abk5 |
publisher |
Elsevier |
series |
Journal of Pharmacological Sciences |
issn |
1347-8613 |
publishDate |
2021-04-01 |
description |
Cannabinoid receptors are a potential target for anti-inflammatory and pain therapeutics. There are two subtypes, CB1 and CB2, and Δ9-tetrahydrocannabinol activates both of them, providing an analgesic effect but also psychoactive side effects. The psychoactive side effects are considered to be caused by activation of CB1, but not CB2. ABK5 is a CB2 subtype selective agonist that has a very different structure from known cannabinoid receptor agonists. Here, we report anti-inflammatory effects of ABK5 using the T-cell line Jurkat cells, and antinociceptive effect in an inflammatory pain model in rats. Production of the cytokines IL-2 and TNF-α was measured in stimulated Jurkat cells and MOLT-4 cells, and CXCL12-mediated chemotaxis of Jurkat cells was evaluated by a transwell migration assay. Anti-inflammatory and antinociceptive effects of ABK5 were also evaluated in a hindpaw CFA model in rats. ABK5 significantly decreased production of IL-2 and TNF-α measured as both mRNA and protein levels, and reduced chemotaxis towards CXCL12. It also attenuated edema and increased mechanical threshold in the hindpaw of CFA-treated rats. These results suggest that ABK5 is a good lead compound for the development of potential anti-inflammatory and analgesic agents. |
topic |
Cannabinoid receptor CB2 agonist Pro-inflammatory cytokines Cell migration Anti-inflammation Inflammatory pain |
url |
http://www.sciencedirect.com/science/article/pii/S1347861320301250 |
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