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

Endogenous cannabinoid signaling pathways have been implicated in protection of the brain from hypoxia, ischemia, and trauma, but the mechanism for these protective effects is uncertain. We found that in CB1 cannabinoid receptor knock-out mice, mortality from permanent focal cerebral ischemia was increased, infarct size and neurological deficits after transient focal cerebral ischemia were more severe, cerebral blood flow in the ischemic penumbra during reperfusion was reduced, and NMDA neurotoxicity was increased compared with wild-type littermates. These findings indicate that endogenous cannabinoid signaling pathways protect mice from ischemic stroke by a mechanism that involves CB1 receptors, and suggest that both blood vessels and neurons may be targets of this protective effect.
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PMID:Increased severity of stroke in CB1 cannabinoid receptor knock-out mice. 1242 32

Whether cannabinoids act as neuroprotectants or, on the contrary, even worsen neuronal damage after cerebral ischemia is currently under discussion. We have previously shown that treatment with the cannabinoid (CB1) receptor antagonist SR141716A reduces infarct volume by approximately 40% after experimental stroke. Since it is suggested that SR141716A may exert neuroprotection besides its cannabinoid receptor-blocking effect, we addressed the question whether SR141716A may act via modulation of postischemic ligand binding to excitatory NMDA and/or alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid (AMPA) receptors. For this purpose, rats (n = 12) were treated with either intravenous saline (control) or CB1 receptor antagonist SR141716A (1 mg/kg) 30 min after permanent middle cerebral artery occlusion. Five hours after ischemia, quantitative receptor autoradiography was performed using [(3)H]CP 55,940, [(3)H]MK-801, and [(3)H]AMPA for labeling of CB1, NMDA, and AMPA receptors, respectively. Ligand binding was analyzed within the infarct core, cortical penumbra, and corresponding areas of the contralateral hemisphere and compared to that of sham-operated rats (n = 5). Both in ischemic controls and SR141716A-treated rats [(3)H]CP 55,940 ligand binding was not specifically regulated in the cortical penumbra or contralateral cortex. Importantly, reduced infarct volumes in SR141716A-treated rats were associated with maintained [(3)H]MK-801 binding to excitotoxic NMDA receptors in the penumbra, compared to a decrease in the control group. In summary, our data suggest that SR141716A may possess additional intrinsic neuroprotective properties independent of receptor-coupled pathways or due to action as a partial agonist.
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PMID:Neuroprotective cannabinoid receptor antagonist SR141716A prevents downregulation of excitotoxic NMDA receptors in the ischemic penumbra. 1687 4

It is well documented that cannabinoid receptor agonist WIN 55,212-2 had protective effect against cerebral ischemic injury. Our previous study indicated that WIN 55,212-2 pretreatment induced ischemic tolerance to focal cerebral ischemia in a dose-dependent manner. The aim of the present study was to investigate the time-effect relationship of the WIN 55,212-2 pretreatment and explore the role of phosphorylated extracellular signal-regulated kinase 1/2. Rats were pretreated with 1mg/kg WIN 55,212-2 once a day for 1, 3 and 5 days. Twenty four hours after the end of pretreatment, focal cerebral ischemia was induced by the middle cerebral artery occlusion. Brain ischemic injury was evaluated by neurological function scores and infarction volumes. The effect of U0126, a potent and specific inhibitor of mitogen-activated protein kinase kinase, on WIN 55,212-2 pretreatment was also studied. Moreover, the expression of phosphorylated extracellular signal-regulated kinase 1/2 in the penumbra of ischemic side 4h after reperfusion was investigated by immunohistochemistry and Western blotting. The results showed that WIN 55,212-2 pretreatment can protect the rat brain against transient focal cerebral ischemia injury, and its protective effect was enhanced gradually with increasing numbers of pretreatment, and was partially reversed by U0126. We further found that WIN 55,212-2 pretreatment up-regulated the levels of phosphorylated extracellular signal-regulated kinase 1/2. These findings suggest that the neuroprotective effect of WIN 55,212-2 pretreatment against focal cerebral ischemia is through the activation of extracellular signal-regulated kinases in rats.
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PMID:Neuroprotective effect of WIN 55,212-2 pretreatment against focal cerebral ischemia through activation of extracellular signal-regulated kinases in rats. 2066 50

Electroacupuncture (EA) pretreatment elicits the neuroprotective effect against cerebral ischemic injury through cannabinoid receptor type 1 receptor (CB1R). In current study, we aimed to investigate whether the signal transducer and activator of transcription 3 (STAT3) and manganese superoxide dismutase (Mn-SOD) were involved in the antioxidant effect of EA pretreatment through CB1R. At 2 h after EA pretreatment, focal cerebral ischemic injury was induced by transient middle cerebral artery occlusion for 60 min in C57BL/6 mice. The expression of Mn-SOD in the penumbra was assessed by Western blot and immunoflourescent staining at 2 h after reperfusion. In the presence or absence of Mn-SOD small interfering RNA (siRNA), the neurological deficit score, the infarct volume, the terminal deoxynucleotidyl transferase-mediated dUDP-biotin nick end labeling (TUNEL) staining, and oxidative stress were evaluated. Furthermore, the Mn-SOD protein expression and phosphorylation of STAT3 at Y705 were also determined in the presence and absence of CB1R antagonists (AM251, SR141716) and CB1R agonists (arachidonyl-2-chloroethylamide (ACEA), WIN 55,212-2). EA pretreatment upregulated the Mn-SOD protein expression and Mn-SOD-positive neuronal cells at 2 h after reperfusion. EA pretreatment also attenuated oxidative stress, inhibited cellular apoptosis, and induced neuroprotection against ischemic damage, whereas these beneficial effects of EA pretreatment were reversed by knockdown of Mn-SOD. Mn-SOD upregulation and STAT3 phosphorylation by EA pretreatment were abolished by two CB1R antagonists, while pretreatment with two CB1R agonists increased the expression of Mn-SOD and phosphorylation level of STAT3. Mn-SOD upregulation by EA attenuates ischemic oxidative damage through CB1R-mediated STAT3 phosphorylation in stroke mice, which may represent one new mechanism of EA pretreatment-induced neuroprotection against cerebral ischemia.
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PMID:Mn-SOD Upregulation by Electroacupuncture Attenuates Ischemic Oxidative Damage via CB1R-Mediated STAT3 Phosphorylation. 2543 86