Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.34 (lipoprotein lipase)
 7,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phospholipase C (PLC) and diacylglycerol lipase (DGL) activities were found in guinea pig platelet microsome preparations. No phospholipase A2 (PLA2) activity was detected. RHC 80267 (1,6-di (0-(carbamoyl) cyclohexanone oxime)hexane) inhibited DGL activity (IC50 = 4 uM) from guinea pig platelet microsomes but had no effect on PLC. RHC 80267 inhibited platelet aggregation (IC50 = 11 uM), release of arachidonic acid (AA), its metabolites, and ATP (IC50 = 4.5 uM) when guinea pig platelets were challenged with a low concentration of thrombin. We propose that PLC-DGL is an important enzymatic pathway for the release of AA in guinea pig platelets.
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PMID:Inhibition of the effects of thrombin on guinea pig platelets by the diacylglycerol lipase inhibitor RHC 80267. 309 68

The recently identified diacylglycerol lipase activity in membranes of chromaffin cells from bovine adrenal medulla [24] is now shown to consist of two enzymes working in series. First the predominantly saturated fatty acid in the sn-1-position is split by a diacylglycerol lipase (glycerol ester hydrolase, EC 3.1.1.34). Subsequently the resulting sn-2-monoacylglycerol is split by a monoacylglycerol lipase (glycerol-monoester acylhydrolase, EC 3.1.1.23) which prefers sn-2-arachidonoyl-monoacylglycerol to sn-2-palmitoyl-monoacylglycerol. At pH 4.0 only the diacylglycerol lipase is active, whereas the monoacylglycerol lipase is irreversibly inactivated. At pH 6.0 both enzymes are active. Pretreatment of the membranes at pH 10 leads to the selective inactivation of the diacylglycerol lipase. Both enzymes are Ca2+- and calmodulin-independent and both are partially inhibited by p-bromophenacyl bromide, however, only at relatively high concentrations of the inhibitor. Chlorpromazine inhibits the diacylglycerol lipase to about the same extent as p-bromophenacyl bromide but the monoacylglycerol lipase is less sensitive. The specific diacylglycerol lipase inhibitor RHC 80267 (1,6-di(O-(carbamoyl)cyclohexanone oxime)hexane) only interacts with the first step, i.e. the diacylglycerol lipase.
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PMID:Diacylglycerol breakdown in plasma membranes of bovine chromaffin cells is a two-step mechanism mediated by a diacylglycerol lipase and a monoacylglycerol lipase. 368 85

The diacylglycerol lipase inhibitor, RHC 80267, 1,6-di(O-(carbamoyl)cyclohexanone oxime)hexane, was tested for its ability to block the release of arachidonic acid from human platelets. At a concentration (10 microM) reported to completely inhibit diacylglycerol lipase in fractions of broken platelets, RHC 80267 had no effect on diacylglycerol lipase activity or the release of arachidonic acid from washed human platelets stimulated with collagen. At a high concentration (250 microM), the compound inhibited the formation of arachidonyl-monoacylglycerol by 70% and the release of arachidonate by 60%. However, at this concentration RHC 80267 was found to inhibit cyclooxygenase activity, phospholipase C activity and the hydrolysis of phosphatidylcholine (PC) (presumably by inhibiting phospholipase A2). The phospholipase C inhibition was attributed to the inhibition of prostaglandin H2 formation, as it was alleviated by the addition of the endoperoxide analog, U-46619. PC hydrolysis was only partially restored with U-46619, suggesting that RHC 80267 directly alters phospholipase A2 activity. The inhibition of arachidonate release observed was accounted for by the inhibition of PC hydrolysis. We conclude that RHC 80267, because of its lack of specificity at concentrations needed to inhibit diacylglycerol lipase, is an unsuitable inhibitor for studying the release of arachidonic acid in intact human platelets.
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PMID:The inhibition of arachidonic acid metabolism in human platelets by RHC 80267, a diacylglycerol lipase inhibitor. 642 15