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)

2-Arachidonyl-glycerol (2-Ara-Gl) recently was identified as a putative endogenous ligand for cannabinoid receptor types CB1 and CB2 by competitive binding. More recent immune function assays demonstrated that 2-Ara-Gl possessed immunomodulatory activity. Because several plant-derived cannabinoids inhibit interleukin-2 (IL-2) expression, 2-Ara-Gl was investigated for its ability to modulate this cytokine. The direct addition of 2-Ara-Gl to mouse splenocyte cultures suppressed phorbol-12-myristate-13-acetate plus ionomycin-induced IL-2 secretion and steady state mRNA expression in a dose-dependent manner. 2-Ara-Gl also produced a marked inhibition of IL-2 promotor activity as determined by transient transfection of EL4.IL-2 cells with a pIL-2-CAT construct. 2-Ara-Gl at 5, 10, 20, and 50 microM suppressed phorbol-12-myristate-13-acetate plus ionomycin-induced IL-2 promotor activity by 18%, 28%, 39%, and 54%, respectively. To further characterize the mechanism for the transcriptional regulation of IL-2 by 2-Ara-Gl, the DNA-binding activity of transcription factors, nuclear factor of activated T cells (NF-AT), nuclear factor for immunoglobulin kappa chain in B cells (NF-kappa B/Rel), activator protein-1(AP-1), octamer, and cAMP-response element binding protein was evaluated by electrophoretic mobility shift assay in mouse splenocytes. In addition, a reporter gene expression system for p(NF-kappa B)3-CAT, p(NF-AT)3-CAT, and p(AP-1)3-CAT was used in transiently transfected EL4.IL-2 cells to determine the effect of 2-Ara-Gl on promoter activity for each of the specific transcription factors. 2-Ara-Gl reduced both the NF-AT-binding and promoter activity in a dose-dependent manner and, to a lesser degree, NF-kappa B/Rel-binding and promoter activity. No significant effect was observed on octamer- and cAMP-response element-binding activity. AP-1 DNA-binding activity was not inhibited by 2-Ara-Gl, but a modest inhibition of promoter activity was observed.
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PMID:Suppression of interleukin-2 by the putative endogenous cannabinoid 2-arachidonyl-glycerol is mediated through down-regulation of the nuclear factor of activated T cells. 954 58

Vascular dementia is the highly devastating neurodegenerative disorder after Alzheimer's disease (AD) and mainly found in aged people but the effectual therapeutic target is still not there. Chronic cerebral hypoperfusion (CCH) has been broadly found in vascular dementia (VaD) patients. CCH is thought to link with neurodegenerative disorders and their subsequent cognitive deteriorate on. This study has been framed to examine the role of a selective agonist of cannabinoid receptor type 2(CB2); 1-phenylisatin in CCH induced VaD. Permanent bilateral common carotid arteries ligation or two vessels occlusion (2VO) technique was used to induce CCH in rats. 2VO animals have shown significant impairment in learning-memory (Morris water maze) and in executive functioning (Attentional set-shifting test). These animals have shown a considerable reduction in brain oxidative stress (thiobarbituric reactive acid substance-TBARS; glutathione-GSH; catalase-CAT and superoxide dismutase-SOD), mitochondrial dysfunction (complexes I, II, IV) with a significant enhancement in cholinergic activity- AChE and brain infarct size2,3,5-triphenylterazolium chloride staining (TTC staining). Animals treated with 2VO have also demonstrated a considerable augmentation in brain edema (water content). Oral administration of 1-phenylisatin has significantly recuperated 2VO induced impairment in learning-memory, an increase in TBARS, GSH, CAT, SOD, mitochondrial activity with a significant reduction in AChE activity and brain damage. Administration of 1- phenylisatin has also reported recovering brain edema in these animals. These results indicate that 2VO induced CCH in rats, which was attenuated with the treatment of 1-phenylisatin. Hence, it may be suggested that modulation of cannabinoid receptor may provide benefits in CCH as cognitive impairment and VaD. Therefore, selective agonists of CB2 receptors may be a potential research target for the alleviation of VaD.
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PMID:Selective Modulator of Cannabinoid Receptor Type 2 Reduces Memory Impairment and Infarct Size During Cerebral Hypoperfusion and Vascular Dementia. 2758 43

Vascular dementia is the second most common cause of cognitive decline in aged people but the effectual therapeutic target is still missing. Chronic cerebral hypoperfusion (CCH) has been widely found in vascular dementia (VaD) patients. CCH is thought to link with neurodegenerative disorders and their subsequent cognitive impairment. The present study has been framed to investigate the role of selective agonist of CB2 receptor (1-phenylisatin) in CCH induced VaD. Permanent bilateral common carotid arteries ligation or two vessels occlusion (2VO) technique was used to induce CCH in rats. 2VO animals have shown significant impairment in learning-memory (Morris water maze) and in executive functioning (Attentional set shifting test). These animals have shown a considerable reduction in brain oxidative stress (thiobarbituric reactive acid substance-TBARS; glutathione-GSH; catalase-CAT and superoxide dismutase-SOD), mitochondrial complex activity (complexes I, II, IV) with the enhancement in cholinergic activity- AChE and brain infarct size (TTC staining). These animals have also shown a considerable increase in brain edema (water content). Oral administration of 1-phenylisatin has significantly recuperated 2VO induced impairment in learning-memory, increase in TBARS, GSH, CAT, SOD, mitochondrial activity with a significant reduction in AChE activity and brain damage. Administration of 1-phenylisatin has also been reported to recover brain edema in these animals. These results indicate that 2VO induced CCH in rats, which was attenuated with the treatment of 1-phenylisatin. Hence, it may be suggested that modulation in cannabinoid receptor may provide benefits in CCH as cognitive impairment and VaD. Therefore, pharmacological positive modulation of CB2 receptors may be a potential research target for alleviation of VaD.
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PMID:Selective modulator of cannabinoid receptor type 2 (CB2) against biochemical alterations and brain damage in chronic cerebral hypoperfusion induced vascular dementia. 2759 83