Tolan, D and Conway, A M and Pyne, N J and Pyne, S (1997) Sphingosine prevents diacylglycerol signaling to mitogen-activated protein kinase in airway smooth muscle. American Journal of Physiology, 273 (3). C928-936. ISSN 0002-9513Full text not available in this repository. (Request a copy from the Strathclyde author)
Because many agonists utilize diacylglycerol (DAG) to initiate nuclear transcriptional activity via protein kinase C (PKC), we have investigated whether sphingosine might counter DAG. Sphingosine inhibited PKC activity in an isolated airway smooth muscle cell lysate and prevented the activation of mitogen-activated protein kinase (MAPK) by platelet-derived growth factor, bradykinin, and phorbol 12-myristate 13-acetate in intact cells. MAPK activation in response to all the agonists involves PKC. The stimulation of [3H]palmitate-labeled cells with sphingosine, in the presence of butan-1-ol (0.3%, vol/vol), induced an increase in [3H]phosphatidate (PtdOH) but was without effect on [3H]DAG. [3H]PtdOH synthesis was inhibited, whereas [3H]DAG levels were increased in the presence of the DAG kinase inhibitor R-59949, indicating that sphingosine stimulates phospholipase C/DAG kinase. Recycling of DAG from PtdOH was prevented by a sphingosine-dependent inhibition of PtdOH phosphohydrolase-2 activity. In conclusion, the sphingosine-induced conversion of DAG to PtdOH may serve to optimize the effect of sphingosine on MAPK. This may account for the antiproliferative action of sphingosine.
|Keywords:||1-butanol, animals, bradykinin, butanols, calcium-calmodulin-dependent protein kinases, cells, cultured, diacylglycerol kinase, diglycerides, enzyme activation, enzyme inhibitors, guinea pigs, kinetics, muscle, smooth, palmitic acid, phosphatidate phosphatase, phosphotransferases (alcohol group acceptor), piperidines, platelet-derived growth factor, protein kinase C, quinazolines, quinazolinones, signal transduction, sphingosine, tetradecanoylphorbol acetate, trachea, Pharmacy and materia medica, Experimental and Cognitive Psychology|
|Subjects:||Medicine > Pharmacy and materia medica|
|Department:||Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences|
|Depositing user:||Pure Administrator|
|Date Deposited:||15 Nov 2011 15:14|
|Last modified:||04 May 2016 20:26|