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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1998-10-5
pubmed:abstractText
We investigated the effects of D1 dopamine receptor stimulation on the activation of mitogen-activated protein kinases (MAPKs) in SK-N-MC human neuroblastoma cells. We found that the D1 dopamine receptor agonist SKF38393 induced similar time- and dose-related activation of p38 MAPK and c-Jun amino-terminal kinase (JNK), whereas extracellular signal-regulated kinase activity was not affected by D1 dopamine receptor stimulation. Maximal stimulation of p38 MAPK and JNK was observed after a 15-min incubation with 100 microM SKF38393. In contrast, 10 microM quinpirole, a D2 dopamine receptor agonist, did not activate p38 MAPK or JNK. Treatment of cells with 10 muM SCH23390, a D1 dopamine receptor antagonist, significantly inhibited the activation of both kinases by SKF38393. These results indicate that activation of the p38 MAPK and JNK signaling pathways is mediated by dopamine D1 receptors in SK-N-MC neuroblastoma cells. Furthermore, dibutyryl-cAMP mimicked SKF38393-mediated stimulation of p38 MAPK and JNK. Inhibition of protein kinase A by 1 microM H-89 or 10 microM adenosine 3', 5'-cyclic monophosphothioate (Rp-isomer, triethylammonium salt) markedly attenuated the activation of p38 MAPK and JNK. Conversely, the selective protein kinase C inhibitor calphostin C did not block D1 dopamine receptor-stimulated activation of p38 MAPK and JNK. These results demonstrate, for the first time, that the Gs-coupled D1 dopamine receptor activates the p38 MAPK and JNK signaling pathways by a protein kinase A-dependent mechanism.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
453-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:9730903-2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine, pubmed-meshheading:9730903-Calcium-Calmodulin-Dependent Protein Kinases, pubmed-meshheading:9730903-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:9730903-Dopamine Agonists, pubmed-meshheading:9730903-Enzyme Activation, pubmed-meshheading:9730903-Humans, pubmed-meshheading:9730903-JNK Mitogen-Activated Protein Kinases, pubmed-meshheading:9730903-Kinetics, pubmed-meshheading:9730903-Mitogen-Activated Protein Kinases, pubmed-meshheading:9730903-Neuroblastoma, pubmed-meshheading:9730903-Phenanthridines, pubmed-meshheading:9730903-Phosphorylation, pubmed-meshheading:9730903-Receptors, Dopamine D1, pubmed-meshheading:9730903-Tumor Cells, Cultured, pubmed-meshheading:9730903-p38 Mitogen-Activated Protein Kinases
pubmed:year
1998
pubmed:articleTitle
D1 dopamine receptor agonists mediate activation of p38 mitogen-activated protein kinase and c-Jun amino-terminal kinase by a protein kinase A-dependent mechanism in SK-N-MC human neuroblastoma cells.
pubmed:affiliation
Laboratory of Molecular Pharmacology, Department of Pharmacology, MCP-Hahnemann School of Medicine, Allegheny University of the Health Sciences, Philadelphia, Pennsylvania 19129, USA. friedmane@auhs.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.