Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P21554 (cannabinoid receptor)
 3,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the effects of two cannabinoid receptor agonists, WIN 55,212-2 and cannabinol, on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in the C6 glioma cell line. After 24 h of lipopolysaccharide (LPS) (1 microg/mL) and interferon-gamma (IFN-gamma) (300 U/mL) stimulation, a significant increase in NO production, evaluated as nitrite, was observed in the culture medium. WIN 55,212-2 (0.1-10000 nM) and cannabinol (0.3-30000 nM), dose-dependently inhibited nitrite production showing a different potency (WIN 55,212-2 EC(50): 4.2 nM; cannabinol EC(50): 700 nM). WIN 55,212-2 (100 nM), given concomitantly to the stimulus also inhibited iNOS expression but had no effect when added to the cells 2 h after LPS/IFN-gamma, indicating a possible interference at the protein synthesis level or at an earlier step, as gene transcription. The cannabinoid CB1 receptor antagonist, SR141716A (0.1-100 nM), but not the cannabinoid CB2 receptor antagonist, SR144528 (0.1-100 nM), reduced in a dose-related manner WIN 55,212-2-and cannabinol-induced inhibition of nitrite production. SR141161A also reversed the WIN 55,212-2-induced inhibition of iNOS expression. These data suggest that selective cannabinoid CB1 receptor activation, by inhibiting iNOS expression and NO overproduction in glial cells, might be helpful in NO-mediated inflammation leading to neurodegeneration.
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PMID:Selective cannabinoid CB1 receptor-mediated inhibition of inducible nitric oxide synthase protein expression in C6 rat glioma cells. 1152 Sep 4

This review examines evidence that delta(9)-tetrahydrocannabinol (THC) can regulate and suppress human immune responses. Leukocytes express both cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2), and levels of mRNA encoding for them are increased in peripheral blood leukocytes obtained from marijuana smokers, suggesting cannabinoid receptor activation in vivo. Exposure of human T-cells to THC suppresses their proliferation, inhibits the release of interferon-gamma, and skews the balance of T-helper cytokines towards a type 2 response. The majority of these effects are CB2 receptor-dependent. Consistent with an impact of THC on cell-mediated immunity, alveolar macrophages (AMs) recovered from the lungs of marijuana smokers are suppressed in their ability to release pro-inflammatory cytokines and nitric oxide (NO), and kill bacteria. Macrophage function is restored by treatment with interferon-gamma, a type 1 cytokine. Habitual exposure to THC appears capable of impacting on human cell-mediated immunity and host defense.
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PMID:Effects of delta-9-tetrahydrocannabinol on human immune function and host defense. 1250 3

2-Arachidonoyl-glycerol (2-AG), an endogenous ligand for cannabinoid receptor types 1 and 2 (CB1 and CB2), has previously been demonstrated to modulate immune functions including suppression of interleukin-2 expression and nuclear factor of activated T cells (NFAT) activity. The objective of the present studies was to investigate the effect of 2-AG on interferon-gamma (IFN-gamma) expression and associated upstream signaling events. Pretreatment of splenocytes with 2-AG markedly suppressed phorbol 12-myristate 13-acetate plus calcium ionophore (PMA/Io)-induced IFN-gamma secretion. In addition, 2-AG suppressed IFN-gamma steady-state mRNA expression in a concentration-dependent manner. To unequivocally determine the putative involvement of CB1 and CB2, splenocytes derived from CB1(-/-)/CB2(-/-) knockout mice were used. No difference in the magnitude of IFN-gamma suppression by 2-AG in wild-type versus CB1/CB2 null mice was observed. Time-of-addition studies revealed that 2-AG treatment up to 12 h post-cellular activation resulted in suppression of IFN-gamma, which was consistent with a time course conducted with cyclosporin A, an inhibitor of NFAT activity. Coincidentally, 2-AG perturbed the nuclear translocation of NFAT protein and blocked thapsigargin-induced elevation in intracellular calcium, suggesting that altered calcium regulation might partly explain the suppression of NFAT nuclear translocation and subsequent IFN-gamma production. Indeed, Io partially attenuated the 2-AG-induced suppression of PMA/Io-stimulated IFN-gamma production. Taken together, these data demonstrate that 2-AG suppresses IFN-gamma expression in murine splenocytes in a CB receptor-independent manner and that the mechanism partially involves suppression of intracellular calcium signaling and perturbation of NFAT nuclear translocation.
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PMID:2-Arachidonoyl-glycerol suppresses interferon-gamma production in phorbol ester/ionomycin-activated mouse splenocytes independent of CB1 or CB2. 1577 49

Atherosclerosis is a chronic inflammatory disease, and is the primary cause of heart disease and stroke in Western countries. Derivatives of cannabinoids such as delta-9-tetrahydrocannabinol (THC) modulate immune functions and therefore have potential for the treatment of inflammatory diseases. We investigated the effects of THC in a murine model of established atherosclerosis. Oral administration of THC (1 mg kg(-1) per day) resulted in significant inhibition of disease progression. This effective dose is lower than the dose usually associated with psychotropic effects of THC. Furthermore, we detected the CB2 receptor (the main cannabinoid receptor expressed on immune cells) in both human and mouse atherosclerotic plaques. Lymphoid cells isolated from THC-treated mice showed diminished proliferation capacity and decreased interferon-gamma secretion. Macrophage chemotaxis, which is a crucial step for the development of atherosclerosis, was also inhibited in vitro by THC. All these effects were completely blocked by a specific CB2 receptor antagonist. Our data demonstrate that oral treatment with a low dose of THC inhibits atherosclerosis progression in the apolipoprotein E knockout mouse model, through pleiotropic immunomodulatory effects on lymphoid and myeloid cells. Thus, THC or cannabinoids with activity at the CB2 receptor may be valuable targets for treating atherosclerosis.
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PMID:Low dose oral cannabinoid therapy reduces progression of atherosclerosis in mice. 1581 11