|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
5
|
|
pubmed:dateCreated |
1996-7-5
|
|
pubmed:abstractText |
We have characterized the mechanism whereby a G protein-coupled receptor, the alpha 1-adrenergic receptor, promotes cellular AA release via the activation of phospholipase A2 (PLA2) in Madin-Darby canine kidney (MDCK-D1) cells. Stimulation of cells with the receptor agonist epinephrine or with the protein kinase C (PKC) activator PMA increased AA release in intact cells and the activity of PLA2 in subsequently prepared cell lysates. The effects of epinephrine were mediated by alpha 1-adrenergic receptors since they were blocked by the alpha 1-adrenergic antagonist prazosin. Epinephrine- and PMA-promoted AA release and activation of the PLA2 were inhibited by AACOCF3, an inhibitor of the 85-kD cPLA2. The 85-kD cPLA2 could be immunoprecipitated from the cell lysate using a specific anti-cPLA2 serum. Enhanced cPLA2 activity in cells treated with epinephrine or PMA could be recovered in such immunoprecipitates, thus directly demonstrating that alpha 1-adrenergic receptors activate the 85-kD cPLA2. Activation of cPLA2 in cell lysates by PMA or epinephrine could be reversed by treatment of lysates with exogenous phosphatase. In addition, both PMA and epinephrine induced a molecular weight shift, consistent with phosphorylation, as well as an increase in activity of mitogen-activated protein (MAP) kinase. The time course of epinephrine-promoted activation of MAP kinase preceded that of the accumulation of released AA and correlated with the time course of cPLA2 activation. Down-regulation of PKC by overnight incubation of cells with PMA or inhibition of PKC with the PKC inhibitor sphingosine blocked the stimulation of MAP kinase by epinephrine and, correspondingly, epinephrine-promoted AA release was inhibited under these conditions. Similarly, blockade of MAP kinase stimulation by the MAP kinase cascade inhibitor PD098059 inhibited epinephrine-promoted AA release. The sensitivity to Ca2+ was similar, although the maximal activity of cPLA2 was enhanced by treatment of cells with epinephrine or PMA. The data thus demonstrate that in MDCK-D1 cells alpha 1-adrenergic receptors regulate AA release through phosphorylation-dependent activation of the 85-kD cPLA2 by MAP kinase subsequent to activation of PKC. This may represent a general mechanism by which G protein-coupled receptors stimulate AA release and formation of products of AA metabolism.
|
|
pubmed:grant |
|
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-1346649,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-13671378,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-1397331,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-1608472,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-1631101,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-1653734,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-1662616,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-1846614,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-1848662,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-2156016,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-2549387,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-2655580,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-2842326,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-2874145,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-3031065,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-3074393,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-533865,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-6810878,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-7601337,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-7644477,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-7814408,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-7836470,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-7903416,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-7908059,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-7989342,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-8018213,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-8034572,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-8034717,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-8042847,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-8043009,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-8077240,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-8155724,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-8166641,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-8175726,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-8226727,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-8227003,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-8232229,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-8253817,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-8294438,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-8300648,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-8380583,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-8381049,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-8407892,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-8408042,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8636443-8419361
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
AIM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Mar
|
|
pubmed:issn |
0021-9738
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
1
|
|
pubmed:volume |
97
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
1302-10
|
|
pubmed:dateRevised |
2009-11-18
|
|
pubmed:meshHeading |
pubmed-meshheading:8636443-Animals,
pubmed-meshheading:8636443-Arachidonic Acid,
pubmed-meshheading:8636443-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:8636443-Cells, Cultured,
pubmed-meshheading:8636443-Cytosol,
pubmed-meshheading:8636443-Dogs,
pubmed-meshheading:8636443-Enzyme Activation,
pubmed-meshheading:8636443-Kidney,
pubmed-meshheading:8636443-Phospholipases A,
pubmed-meshheading:8636443-Phospholipases A2,
pubmed-meshheading:8636443-Phosphorylation,
pubmed-meshheading:8636443-Protein Kinase C,
pubmed-meshheading:8636443-Receptors, Adrenergic, alpha-1
|
|
pubmed:year |
1996
|
|
pubmed:articleTitle |
Protein kinase C-dependent activation of cytosolic phospholipase A2 and mitogen-activated protein kinase by alpha 1-adrenergic receptors in Madin-Darby canine kidney cells.
|
|
pubmed:affiliation |
Department of Pharmacology, University of California at San Diego, La Jolla, California 92093, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|
