Diacylglycerol in the synergy of bradykinin and thrombin stimulation of prostaglandin synthesis.
Simultaneous addition of bradykinin and thrombin to 3T3 fibroblasts for 5 min resulted in less than additive stimulation of prostaglandin E2 synthesis. However, if cells were stimulated with either agonist alone, then the other added 15 min later, prostaglandin E2 synthesis was synergistically enhanced. In contrast, if either agonist was added, then prostaglandin E2 synthesis in response to the same agonist assessed 15 min later, synthesis was markedly reduced. Bradykinin and thrombin caused increased diacylglycerol accumulation in the cells, and addition of the diacylglycerol kinase inhibitor R59022 dramatically increased the effects of sequential addition of the agonists. These results suggest that diacylglycerol generated in response to activation of one receptor amplifies the effects of activation of other receptors.
Burch
R M
RM
Nova Pharmaceutical Corporation, Baltimore, MD 21224.
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D003512:Cyclohexanones / Q000494:pharmacology; D019852:Diacylglycerol Kinase; D004075:Diglycerides / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis*; D004357:Drug Synergism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005989:Glycerides / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010770:Phosphotransferases / Q000037:antagonists & inhibitors; D011744:Pyrimidinones / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology*; D013997:Time Factors
D003512:Cyclohexanones; D004075:Diglycerides; D005989:Glycerides; D011744:Pyrimidinones; D013844:Thiazoles; C036535:1,6-bis(cyclohexyloximinocarbonyl)hexane; C047505:R 59022; D010770:Phosphotransferases; D019852:Diacylglycerol Kinase; D013917:Thrombin; D015232:Dinoprostone; D001920:Bradykinin