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101.
Gaewon Nam Se Kyoo Jeong Bu Man Park Sin Hee Lee Hyun Jong Kim Seung-Phil Hong Beomjoon Kim Bong-Woo Kim 《ANNALS OF DERMATOLOGY》2016,28(1):22-29
BackgroundMany inflammatory mediators, including various cytokines (e.g. interleukins and tumor necrosis factor [TNF]), inflammatory proteases, and histamine are released following mast cell activation. However, the endogenous modulators for mast cell activation and the underlying mechanism have yet to be elucidated. Endogenous cannabinoids such as palmitoylethanolamide (PEA) and N-arachidonoylethanolamine (anandamide or AEA), were found in peripheral tissues and have been proposed to possess autacoid activity, implying that cannabinoids may downregulate mast cell activation and local inflammation.ObjectiveIn order to investigate the effect of cannabinoid receptor-1 (CB1R) agonists on mast cell activation, AEA-derived compounds were newly synthesized and evaluated for their effect on mast cell activation.MethodsThe effects of selected compounds on FcεRI-induced histamine and β-hexosaminidase release were evaluated in a rat basophilic leukemia cell line (RBL-2H3). To further investigate the inhibitory effects of CB1R agonist in vivo, an oxazolone-induced atopic dermatitis mouse model was exploited.ResultsWe found that CB1R inhibited the release of inflammatory mediators without causing cytotoxicity in RBL-2H3 cells and that CB1R agonists markedly and dose-dependently suppressed mast cell proliferation indicating that CB1R plays an important role in modulating antigen-dependent immunoglobulin E (IgE)-mediated mast cell activation. We also found that topical application of CB1R agonists suppressed the recruitment of mast cells into the skin and reduced the level of blood histamine.ConclusionOur results indicate that CB1R agonists down-regulate mast cell activation and may be used for relieving inflammatory symptoms mediated by mast cell activation, such as atopic dermatitis, psoriasis, and contact dermatitis. 相似文献
102.
杨红卫 《山东大学学报(医学版)》2009,47(9):17-20
目的探讨大麻素受体1(CB1)在四氢大麻酚(Δ9 THC)抑制CA1区长时程抑制(LTD)中的作用。方法在小鼠腹腔注射Δ9 THC(10?mg/kg)或CB1受体的选择性抑制剂SR141716(SR,5?mg/kg)24?h后切片,在海马CA1区记录场电位EPSP。结果①给予低频电刺激(1?Hz 15?min)诱导CA1区LTD,Δ9 THC可显著降低LTD(P<0.01);②Δ9 THC显著降低LTD的效应可被CB1的选择性抑制剂SR所翻转;③在CB1基因敲除的小鼠,Δ9 THC对LTD的效应与溶剂对照组相比无统计学差异(P>0.05)。结论CB1受体介导Δ9 THC抑制离体海马CA1区LTD的作用。 相似文献
103.
Constantin Itin Abraham J. Domb Amnon Hoffman 《Journal of pharmaceutical sciences》2021,110(4):1863-1864
Contrary to human, porcine mucosa of the inner side of the lip is parakeratinized. Thus, although desirable due to its large surface area, it does not closely resemble human buccal mucosa to be considered a suitable model for systemic drug delivery research. Nevertheless, it can be utilized for comparative screening of topical or systemic delivery of bioactive agents, mostly lipophilic such as cannabinoids. 相似文献
104.
New neurons are continuously produced by neural stem cells (NSCs) within the adult hippocampus. Numerous diseases, including major depressive disorder and HIV-1 associated neurocognitive disorder, are associated with decreased rates of adult neurogenesis. A hallmark of these conditions is a chronic release of neuroinflammatory mediators by activated resident glia. Recent studies have shown a neuroprotective role on NSCs of cannabinoid receptor activation. Yet, little is known about the effects of GPR55, a candidate cannabinoid receptor, activation on reductions of neurogenesis in response to inflammatory insult. In the present study, we examined NSCs exposed to IL-1β in vitro to assess inflammation-caused effects on NSC differentiation and the ability of GPR55 agonists to attenuate NSC injury. NSC differentiation and neurogenesis was determined via immunofluorescence and flow cytometric analysis of NSC markers (Nestin, Sox2, DCX, S100β, βIII Tubulin, GFAP). GPR55 agonist treatment protected against IL-1β induced reductions in neurogenesis rates. Moreover, inflammatory cytokine receptor mRNA expression was down regulated by GPR55 activation in a neuroprotective manner. To determine inflammatory responses in vivo, we treated C57BL/6 and GPR55−/− mice with LPS (0.2 mg/kg/day) continuously for 14 days via osmotic mini-pump. Reductions in NSC survival (as determined by BrdU incorporation), immature neurons, and neuroblast formation due to LPS were attenuated by concurrent direct intrahippocampal administration of the GPR55 agonist, O-1602 (4 µg/kg/day). Molecular analysis of the hippocampal region showed a suppressed ability to regulate immune responses by GPR55−/− animals manifesting in a prolonged inflammatory response (IL-1β, IL-6, TNFα) after chronic, systemic inflammation as compared to C57BL/6 animals. Taken together, these results suggest a neuroprotective role of GPR55 activation on NSCs in vitro and in vivo and that GPR55 provides a novel therapeutic target against negative regulation of hippocampal neurogenesis by inflammatory insult. 相似文献
105.
106.
Jolanta Weresa Anna Pędzińska-Betiuk Rafał Kossakowski Barbara Malinowska 《Pharmacological reports : PR》2019,71(1):82-89
Background
Drugs targeting CB1 and CB2 receptors have been suggested to possess therapeutic benefit in cardiovascular disorders associated with elevated sympathetic tone. Limited data suggest cannabinoid ligands interact with postsynaptic β-adrenoceptors. The aim of this study was to examine the effects of CB1 and CB2 antagonists, AM251 and AM630, respectively, at functional cardiac β-adrenoceptors.Methods
Experiments were carried out in isolated spontaneously beating right atria and paced left atria where inotropic and chronotropic increases were induced by isoprenaline and selective agonists of β1 and β2-adrenergic receptors.Results
We found four different effects of AM251 and AM630 on the cardiostimulatory action of isoprenaline: (1) both CB receptor antagonists 1 μM enhanced the isoprenaline-induced increase in atrial rate, and AM630 1 μM enhanced the inotropic effect of isoprenaline; (2) AM251 1 μM decreased the efficacy of the inotropic effect of isoprenaline; (3) AM251 0.1 and 3 μM and AM630 3?μM reduced the isoprenaline-induced increases in atrial rate; (4) AM630 0.1 and 3?μM enhanced the inotropic effect of isoprenaline, which was not changed by the same concentrations of AM251.Conclusions
Our results show that the CB1 and CB2 receptor antagonists AM251 and AM630 have bidirectional effects on the cardiostimulatory action of isoprenaline, most likely related to an interaction with β1-adrenoceptors. Provided that the results translate to human heart, caution should be taken when using CB1 and CB2 receptor antagonists, as an enhanced sympathetic tone accompanies many cardiovascular disorders. 相似文献107.
Cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2) are important members of G protein-coupled receptors (GPCRs). Numerous studies have shown that CB1 receptor can form heterodimers with dopamine receptors (D2), μ-opioid receptor (μOR), orexin-1 receptor, adenosine receptor (A2A) or β2 adrenergic receptors, and then forming an essential functional entity. This review summarizes the research progress on heterodimers of cannabinoid CB1 or CB2, the function of heterodimers as well as the downstream signalings. The different pharmacological properties of the receptor heterodimer lead to bringing a change in receptor pharmacology, which will have a profound impact on drug development. 相似文献
108.
Rola M. Labib Radhakrishnan Srivedavyasasri Fadia S. Youssef Samir A. Ross 《Saudi Pharmaceutical Journal》2018,26(3):437-444
Pinus roxburghii is highly popular as a potent analgesic and anti-inflammatory agent; however its exact mechanism of action was not fully elucidated. We aimed to interpret the analgesic and anti-inflammatory activity of the total ethanol extract of Pinus roxburghii bark (PRE) and its isolated compounds by both in silico molecular modelling and in-vitro cannabinoid and opioid binding activities evaluation for the first time. Comprehensive phytochemical investigation of PRE resulted in the isolation of sixteen compounds that were fully elucidated using 1H NMR and 13C NMR. Four of which namely 1,3,7-trihydroxyxanthone (1), 2,4,7-trihydroxyxanthone (2), isopimaric acid (9) and 3-methoxy-14-serraten-21-one (10) were first to be isolated from PRE. In silico molecular modelling was done using Accelry’s discovery studio 2.5 on the cannabinoid receptor (CB1) and the different opioid receptors (mu, kappa and delta). Results showed that the different isolated constituents exhibited variable degrees of binding with the different examined receptors that undoubtedly explained the observed analgesic and anti-inflammatory activity of PRE. Thus in vitro evaluation of cannabinoid (CB1, CB2) and opioid (μ, κ, δ) binding activities for the isolated compounds was done. PRE and ursolic acid (11) showed a good CB1 receptor binding activity with 66.8 and 48.1% binding, respectively. Isopimaric acid (9) showed good CB2 and mu receptors binding activity estimated by 58.1 and 29.1% binding, respectively. Meanwhile, querectin-3-O-rhamnoside (7) exhibited a moderate κ-opioid receptor activity showing 56.0% binding. Thus, PRE could offer a natural analgesic and anti-inflammatory candidate through the synergistic action of all its components. 相似文献
109.
110.
The effects of cannabinoids on synaptic transmission were measured optically in rat hippocampal cultures. Synaptic release sites were labeled with the fluorescent dye FM1-43 in a stimulus-dependent manner. Action potential-induced release of FM1-43 required extracellular Ca2+ and was inhibited 65 +/- 3% by blockade of high-threshold voltage-gated Ca2+ channels with omega-grammotoxin SIA (300 nM). The cannabimimetic drug, Win 55212-2 (300 nM), inhibited FM1-43 release by 51 +/- 3%. The inhibition produced by Win55212-2 was blocked by the CB1 cannabinoid receptor antagonist, SR141716 (1 microM). The intensity of FM1-43 labeled puncta ranged 4-fold, although the inhibition produced by Win55212-2 was distributed normally across synaptic sites of various labeling intensities. The FM1-43-based optical method appears promising for the study of the effects of cannabinoids and other drugs on synaptic networks. These results indicate that cannabimimetics act presynaptically to inhibit the release of neurotransmitter and that this inhibition is observed uniformly at boutons of varied activity levels. 相似文献