Inhibition of the effects of thrombin on guinea pig platelets by the diacylglycerol lipase inhibitor RHC 80267.
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.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D002250:Carbon Radioisotopes; D003510:Cyclohexanes / Q000494:pharmacology*; D003512:Cyclohexanones / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors / Q000502:physiology; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D010974:Platelet Aggregation / Q000187:drug effects; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000502:physiology
D001095:Arachidonic Acids; D002250:Carbon Radioisotopes; D003510:Cyclohexanes; D003512:Cyclohexanones; D016718:Arachidonic Acid; C036535:1,6-bis(cyclohexyloximinocarbonyl)hexane; D000255:Adenosine Triphosphate; D008071:Lipoprotein Lipase; D010738:Type C Phospholipases; D013917:Thrombin