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)

The endogenous cannabinoid anandamide, a lipid mediator, induces various physiologic events such as vascular relaxation, inhibition of gap-junctions formation, tumor proliferation, neurologic analgesia, and apoptosis. Although increased concentration of anandamide in plasma has been implicated in pathophysiologic states including endotoxin-induced hypotension, the effects of anandamide on hepatocytes still remain unclear. In this study, we present evidence that plasma anandamide concentration is highly increased in severe hepatitis and cirrhosis patients. In addition, concentrations of anandamide within the pathophysiologic range potently induced apoptosis of hepatoma cell line (Hep G2) and primary hepatocytes, suggesting a possible link between increased anandamide level and hepatocyte damage. Anandamide-induced cell death was preceded by G0/G1 cell-cycle arrest, activation of proapoptotic signaling (i.e., p38 MAPK and JNK), and inhibition of antiapoptotic signaling (i.e., PKB/Akt) pathways. Moreover, anandamide increased susceptibility to oxidative stress-induced hepatocyte damage. In this context, methyl-beta-cyclodextrin (MCD), a membrane cholesterol depletor, or mevastatin, an HMG-CoA reductase inhibitor, or N-acetyl cysteine, an antioxidant, potently inhibited the anandamide-induced proapoptotic events and cell death, whereas putative cannabinoid receptor antagonists did not exhibit an inhibitory effect on anandamide-induced cell death. Furthermore, binding assay using polymyxin beads revealed that anandamide could interact with cholesterol. In conclusion, our data suggest that cholesterol present in the cell membrane determines the fate of hepatocytes exposed to anandamide, possibly functioning as an anandamide receptor.
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PMID:Membrane cholesterol but not putative receptors mediates anandamide-induced hepatocyte apoptosis. 1457 55

The metabolic syndrome increases the risk of atherothrombotic cardiovascular disease (CVD) and diabetes. In turn, diabetes promotes the development of atheroma and is regarded as a coronary heart disease risk equivalent. A multifactorial therapeutic strategy is advocated for patients with the metabolic syndrome to improve cardiovascular risk factor profiles and to reduce the chances of developing type 2 diabetes. Individual components of the syndrome must be addressed using safe, efficacious, and cost-effective measures. There is general agreement that lifestyle modifications, including control of body weight, avoidance of central adiposity, adoption of an antiatherogenic diet, and regular physical activity, are crucial. However, as the magnitude of the individual components of the metabolic syndrome increases with time, lifestyle measures are often insufficient. An individual with metabolic syndrome will often require drug treatment for hyperglycemia, atherogenic dyslipidemia, and high blood pressure, together with antiplatelet therapy. Reducing the need for polypharmacy is an increasingly important consideration for clinicians and the pharmaceutical industry; to date, no single therapy has emerged that targets the root cause(s) of the syndrome. HMG-CoA reductase inhibitors are important agents that reduce CVD morbidity and mortality, in people with impaired fasting glucose or metabolic syndrome. Selective cannabinoid receptor antagonists appear promising because they improve or attenuate several key defects of the syndrome. Thiazolidinediones and metformin are presently licensed for treatment of type 2 diabetes but may prove to have a broader role in future. Novel insulin-sensitizing drugs are under investigation. Drugs that act to prevent or reverse endothelial dysfunction may be of particular utility in preventing cardiovascular disease, especially if initiated before tissue damage has become irreversible. Insulin therapy, which has antiinflammatory and endothelial protective properties, has been shown to reduce morbidity and mortality in high-risk nondiabetic patients during critical illness. Potential synergy between different classes of drugs with metabolic and/or cardiovascular protective properties merits further investigation.
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PMID:Prevention of cardiovascular complications of the metabolic syndrome: focus on pharmacotherapy. 1837 Jul 50