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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
2001-3-6
pubmed:abstractText
The mitogen-activated protein kinase (MAPK) family consists of the p42/p44 MAPKs and the stress-activated protein kinases, c-Jun N-terminal kinase (JNK) and p38 MAPK. We have previously reported that the human adenosine A(1) receptor stimulates p42/p44 MAPK in transfected Chinese hamster ovary cells. In this study, we have investigated whether the endogenous adenosine A(1) receptor in the smooth muscle cell line, DDT(1)MF-2 activates p42/p44 MAPK, JNK and p38 MAPK. The adenosine A(1) receptor agonist N(6)-cyclopentyladenosine stimulated time and concentration-dependent increases in p42/p44 MAPK and p38 MAPK phosphorylation in DDT(1)MF-2 cells. No increases in JNK phosphorylation were observed following adenosine A(1) receptor activation. N(6)-cyclopentyladenosine-mediated increases in p42/p44 MAPK and p38 MAPK phosphorylation were blocked by the selective adenosine A(1) receptor antagonist 1,3-dipropylcyclopentylxanthine and following pretreatment of cells with pertussis toxin. Furthermore, adenosine A(1) receptor-mediated increases in p42/p44 MAPK were sensitive to the MAPK kinase 1 inhibitor PD 98059 (2'-amino-3'-methoxyflavone), whereas p38 MAPK responses were blocked by the p38 MAPK inhibitor SB 203580 (4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole). The broad range protein tyrosine kinase inhibitors genistein and tyrphostin A47 (alpha-cyano-(3,4-dihydroxy)thiocinnamide) did not block adenosine A(1) receptor stimulation of p42/p44 MAPK. For comparison, insulin-mediated increases in p42/p44 MAPK were blocked by genistein and tyrphostin A47. The Src tyrosine kinase inhibitor PP2 (4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine) and the epidermal growth factor receptor tyrosine kinase inhibitor AG1478 (4-(3-chloroanilino)-6,7-dimethoxyquinazoline) also had no effect on adenosine A(1) receptor stimulation of p42/p44 MAPK. Furthermore, the protein kinase C inhibitors Ro 31-8220 (3-[1-[3-(2-isothioureido) propyl]indol-3-yl]-4-(1-methylindol-3-yl)-3-pyrrolin-2,5-dione), chelerythrine and GF 109203X (2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)-maleimide) were without effect on adenosine A(1) receptor-induced p42/p44 MAPK phosphorylation. In contrast, wortmannin and LY 294002 (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one), inhibitors of phosphatidylinositol 3-kinase, attenuated adenosine A(1) receptor stimulation of p42/p44 MAPK phosphorylation. In conclusion, the adenosine A(1) receptor stimulates p42/p44 MAPK through a pathway which appears to be independent of tyrosine kinase activation but involves phosphatidylinositol 3-kinase. Finally, adenosine A(1) receptor stimulation in DDT(1)MF-2 cells also activated p38 MAPK but not JNK via a pertussis toxin-sensitive pathway.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/1,3-dipropyl-8-cyclopentylxanthine, http://linkedlifedata.com/resource/pubmed/chemical/Adenosine, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Hypoglycemic Agents, http://linkedlifedata.com/resource/pubmed/chemical/Insulin, http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein..., http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/N(6)-cyclopentyladenosine, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Purinergic P1, http://linkedlifedata.com/resource/pubmed/chemical/Vasodilator Agents, http://linkedlifedata.com/resource/pubmed/chemical/Xanthines, http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0014-2999
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
413
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
151-61
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:11226388-Adenosine, pubmed-meshheading:11226388-Animals, pubmed-meshheading:11226388-Cell Line, pubmed-meshheading:11226388-Cricetinae, pubmed-meshheading:11226388-Enzyme Inhibitors, pubmed-meshheading:11226388-Hypoglycemic Agents, pubmed-meshheading:11226388-Insulin, pubmed-meshheading:11226388-JNK Mitogen-Activated Protein Kinases, pubmed-meshheading:11226388-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:11226388-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:11226388-Mitogen-Activated Protein Kinases, pubmed-meshheading:11226388-Muscle, Smooth, pubmed-meshheading:11226388-Phosphatidylinositol 3-Kinases, pubmed-meshheading:11226388-Protein Kinase C, pubmed-meshheading:11226388-Protein-Tyrosine Kinases, pubmed-meshheading:11226388-Receptors, Purinergic P1, pubmed-meshheading:11226388-Signal Transduction, pubmed-meshheading:11226388-Vasodilator Agents, pubmed-meshheading:11226388-Xanthines, pubmed-meshheading:11226388-p38 Mitogen-Activated Protein Kinases
pubmed:year
2001
pubmed:articleTitle
Regulation of p42/p44 MAPK and p38 MAPK by the adenosine A(1) receptor in DDT(1)MF-2 cells.
pubmed:affiliation
Department of Life Sciences, Faculty of Science and Mathematics, Nottingham Trent University, Clifton Lane, NG11 8NS, Nottingham, UK
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't