Diacylglycerol and ceramide formation induced by dopamine D2S receptors via Gbeta gamma -subunits in Balb/c-3T3 cells |
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Authors: | Liu Gele Ghahremani Mohammad H Banihashemi Behzad Albert Paul R |
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Institution: | Ottawa Health Research Institute (Neuroscience), University of Ottawa, Canada K1H 8M5. |
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Abstract: | Diacylglycerol (DAG)and ceramide are important second messengers affecting cell growth,differentiation, and apoptosis. Balb/c-3T3 fibroblast cellsexpressing dopamine-D2S (short) receptors (Balb-D2S cells) provide amodel of G protein-mediated cell growth and transformation. In Balb-D2Scells, apomorphine (EC50 = 10 nM) stimulated DAG and ceramide formation by 5.6- and 4.3-fold, respectively, maximal at1 h and persisting over 6 h. These actions were blocked by pretreatment with pertussis toxin (PTX), implicatingGi/Go proteins. To address which G proteins areinvolved, Balb-D2S clones expressing individual PTX-insensitiveG i proteins were treated with PTX and tested forapomorphine-induced responses. Neither PTX-insensitive G i2 nor G i3 rescued D2S-induced DAG orceramide formation. Both D2S-induced DAG and ceramide signals requiredG![beta](http://ajpcell.physiology.org/math/12pt/normal/beta.gif) -subunits and were blocked by inhibitors of phospholipaseC1-(6-(17 ]-3-methoxyestra-1,2,310]-trien- 17yl)amino]hexyl)-1H-pyrrole-2,5-dione(U-73122) and partially by D609]. The similar G protein specificity ofD2S-induced calcium mobilization, DAG, and ceramide formation indicatesa common G![beta](http://ajpcell.physiology.org/math/12pt/normal/beta.gif) -dependent phospholipase C-mediated pathway. Both D2agonists and ceramide specifically induced mitogen-activated proteinkinase (ERK1/2), suggesting that ceramide mediates a novel pathway ofD2S-induced ERK1/2 activation, leading to cell growth. |
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