The cannabinoid CB2 receptor selective agonist JWH133 reduces mast cell oedema in response to compound 48/80 in vivo but not the release of β-hexosaminidase from skin slices in vitro

Jonsson, Kent-Olov; Persson, Emma; Fowler, Christopher J.

doi:10.1016/j.lfs.2005.05.059

Cited by 39 publications

(28 citation statements)

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“…Following this early report, the anti-nociceptive effects of systemic administration of AM1241, JWH015 and GW405833 have been reported in the carrageenan, Freund's complete adjuvant and colonic distention models of inflammatory pain [50,[55][56][57][58]. Similar to the effects of HU308, systemic administration of JWH133 and GW405833 also reduced inflammatory oedema due to carrageenan or the histamine releasing compound 48/80 [57,59]. These effects of systemically administered CB 2 agonists may arise from local peripheral, spinal or possibly supraspinal sites of action (Table 2).…”

Section: Antinociceptive Effects Of Cb 2 Receptor Agonists In Models mentioning

confidence: 82%

Cannabinoid CB2 Receptor-Mediated Anti-nociception in Models of Acute and Chronic Pain

et al. 2007

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The endocannabinoid system consists of cannabinoid CB(1) and CB(2) receptors, endogenous ligands and their synthesising/metabolising enzymes. Cannabinoid receptors are present at key sites involved in the relay and modulation of nociceptive information. The analgesic effects of cannabinoids have been well documented. The usefulness of nonselective cannabinoid agonists can, however, be limited by psychoactive side effects associated with activation of CB(1) receptors. Following the recent evidence for CB(2) receptors existing in the nervous system and reports of their up-regulation in chronic pain states and neurodegenerative diseases, much research is now aimed at shedding light on the role of the CB(2) receptor in human disease. Recent studies have demonstrated anti-nociceptive effects of selective CB(2) receptor agonists in animal models of pain in the absence of CNS side effects. This review focuses on the analgesic potential of CB(2) receptor agonists for inflammatory, post-operative and neuropathic pain states and discusses their possible sites and mechanisms of action.

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Section: Antinociceptive Effects Of Cb 2 Receptor Agonists In Models mentioning

confidence: 82%

Cannabinoid CB2 Receptor-Mediated Anti-nociception in Models of Acute and Chronic Pain

et al. 2007

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“…Given the anti-inflammatory properties of CBD together with the potential, although controversial, of cannabinoids/endocannabinoids to modulate mast cell activation [17][18][19][20][21][22], we questioned here, for the first time, whether CBD affects mast cell function. To this end, we used RBL-2H3 cell cultures, a rat cell line of basophilic-leukemia origin, displaying characteristics of mucosal mast cells, used extensively to study signaling pathways, leading to degranulation and release of inflammatory mediators upon antigen-induced aggregation of the IgE-bound, high-affinity receptors (FcεRIs) expressed on their surface [23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Cannabidiol, unlike synthetic cannabinoids, triggers activation of RBL-2H3 mast cells

Giudice¹,

Rinaldi²,

Passarotto³

et al. 2007

Journal of Leukocyte Biology

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Cannabidiol (CBD), a prominent psychoinactive component of cannabis with negligible affinity for known cannabinoid receptors, exerts numerous pharmacological actions, including anti-inflammatory and immunosuppressive effects, the underlying mechanisms of which remain unclear. In the current study, we questioned whether CBD modulates activation of mast cells, key players in inflammation. By using the rat basophilic leukemia mast cell line (RBL-2H3), we demonstrate that CBD (3-10 muM) augments beta-hexosaminidase release, a marker of cell activation, from antigen-stimulated and unstimulated cells via a mechanism, which is not mediated by G(i)/G(o) protein-coupled receptors but rather is associated with a robust rise in intracellular calcium ([Ca(2+)](i)) levels sensitive to clotrimazole and nitrendipine (10-30 muM). This action, although mimicked by Delta(9)-tetrahydrocannabinol (THC), is opposite to that inhibitory, exerted by the synthetic cannabinoids WIN 55,212-2 and CP 55,940. Moreover, the vanilloid capsaicin, a full agonist of transient receptor potential channel VR1, did not affect [Ca(2+)](i)levels in the RBL-2H3 cells, thus excluding the involvement of this receptor in the CBD-mediated effects. Together, these results support existence of yet-to-be identified sites of interaction, i.e., receptors and/or ion channels associated with Ca(2+) influx of natural cannabinoids such as CBD and THC, the identification of which has the potential to provide for novel strategies and agents of therapeutic interest.

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“…CB2 activation has many different effects on mast cells. JWH-133 reduced edema induced by mast cells (60). HU-308, which is a CB2 agonist, reduced arachidonic acid in ear edema (61).…”

Section: Discussionmentioning

confidence: 96%

Cannabinoid receptor type 2 agonist JWH-133 deteriorates the liver toxicity induced by cypermethrin

2018

Turk J Vet Anim Sci

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IntroductionCYP is a synthetic type II pyrethroid insecticide widely used for the control of ectoparasites of domestic animals and home pest control owing to its high insecticidal potential and lower mammalian toxicity (1). CYP shows its effect via the voltage-dependent Na + and Ca 2+ channels in the membrane of nerve cells (2-4). There is an increasing amount of evidence suggesting toxic effects on nontarget organisms in chronic exposure of CYP (5,6). Several studies have shown that CYP causes oxidative stress, biochemical changes such as increase in activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH); elevation in levels of thiobarbituric acid reactive substances (TBARS), a decrease in activities of the antioxidant enzymes (7,8), and histopathological changes such as vacuolar degeneration, enlarged sinusoid, vacuole formation in hepatocytes, pleomorphism in the nucleus, congestion, necrosis, hepatocellular hypertrophy, multinucleated hepatocytes, mononuclear cell infiltration (MCI), and increase in Kupffer cell numbers (2,6).Marijuana or cannabis, whose main active ingredient is delta-9-tetrahydrocannabinol, activates two G proteincoupled membrane receptors, named CB1 and CB2 (9-11). CB1 is mainly expressed in the nervous system and is less expressed in various peripheral tissues such as the heart, gut, liver, and in cells such as endothelial cells and adipocytes. In comparison, CB2 is largely expressed in immune cells, tonsils, spleen, and testis. Moreover, it has been observed to be expressed to a lesser extent in other tissues and in cells like hepatic myofibroblasts (12).Recent studies have shown the dysregulation of endocannabinoid system in experimental models of bowel, liver, and heart diseases. Evidence suggests that Abstract: Cannabinoid receptor 2 (CB2) has a role in the pathology of some liver diseases. Cypermethrin (CYP) is a synthetic pyrethroid insecticide used commonly for the control of pests and vectors, and for protection of foodstuffs. In this study, the involvement of CB2 in CYP-induced liver damage in rats was investigated. CYP was applied to rats orally at a dose of 125 mg/kg bw per day for 14 days. CB2 agonist JWH-133 was administered by intraperitoneal injection at a dose of 3 mg/kg bw per day for the last 4 days of CYP toxicity. JWH-133 deteriorated the liver damage induced by CYP. JWH-133 increased serum hepatic enzyme activities (aspartate aminotransferase, alanine aminotransferase) in rats given CYP. However, it decreased lipid peroxidation. There were no differences in the levels of hepatic CB2 mRNA among the groups. CB2 receptors were expressed in a small amount in normal liver tissue. In contrast, the expression levels of CB2 in CYPtreated rats were increased in fibrocyte/fibroblast, bile duct epithelial cells, Kupffer cells, and mast cells. In conclusion, CB2 was upregulated in the liver exposed to CYP, predominantly in hepatic fibrogenic cells. JWH-133 enhanced the CYPinduced liver damage by receptor mediated and/or non...

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The cannabinoid CB2 receptor selective agonist JWH133 reduces mast cell oedema in response to compound 48/80 in vivo but not the release of β-hexosaminidase from skin slices in vitro

Cited by 39 publications

References 53 publications

Cannabinoid CB2 Receptor-Mediated Anti-nociception in Models of Acute and Chronic Pain

Cannabinoid CB2 Receptor-Mediated Anti-nociception in Models of Acute and Chronic Pain

Cannabidiol, unlike synthetic cannabinoids, triggers activation of RBL-2H3 mast cells

Cannabinoid receptor type 2 agonist JWH-133 deteriorates the liver toxicity induced by cypermethrin

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