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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2000-5-25
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pubmed:abstractText |
1. Tyrosine kinases have been proposed as regulators of voltage-operated calcium channels. The effects of a range of structurally different inhibitors of protein tyrosine kinases (PTK) were examined on voltage-operated calcium channel currents (I(Ba)) and pp60(c-src) kinase (c-src) activity in vitro. 2. I(Ba) was measured in single myocytes isolated from rabbit ear artery by conventional whole cell voltage-clamp techniques. The activity of purified human c-src was measured in vitro using a non-radioactive assay. 3. Bath application of tyrphostin-23 and genistein (non-selective PTK inhibitors), bistyrphostin (a receptor-PTK-selective inhibitor) and PP1 (a src family-selective inhibitor) inhibited I(Ba) in a concentration-dependent manner over a range of test membrane potentials. Intracellular application of peptide-A, a peptide inhibitor of c-src also inhibited currents. Inhibitor potency series against I(Ba) was PP1 > genistein > tyrphostin 23 > bistyrphostin. 4. Tyrphostin-23, genistein, PP1, and peptide-A shifted the steady-state inactivation curves in a hyperpolarized direction without altering their slope. The inhibitors had no significant effects on I(Ba) activation calculated from current-voltage relationships. 5. The agents inhibited c-src activity in a concentration-dependent manner. The order of potency was PP1 > genistein > peptide-A > tyrphostin-23 > bistyrphostin. The IC(50) for inhibition of c-src activity was similar to the IC(50) for inhibition of I(Ba) in all cases. 6. Western blot analysis with a specific antibody to c-src showed the presence of this cytoplasmic tyrosine kinase in rabbit ear artery cells. 7. A range of structurally dissimilar inhibitors of PTKs inhibit I(Ba) and c-src activity with similar potency. These data provide further evidence implicating endogenous c-src in the modulation of L-type calcium channels in vascular smooth muscle cells.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10742290-1326293,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10742290-1336377,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10742290-1862529,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10742290-2052747,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10742290-2065781,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10742290-2171508,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10742290-2475611,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10742290-2850808,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10742290-7495884,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10742290-7712009,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10742290-7997267,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10742290-8384532,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10742290-8388295,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10742290-8554555,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10742290-8557675,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10742290-8562808,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10742290-8575003,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10742290-8621613,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10742290-8732508,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10742290-8968578,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10742290-8980120,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10742290-9019541,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10742290-9215709,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10742290-9310443,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10742290-9365813,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10742290-9365814,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10742290-9442882,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10742290-9641547,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10742290-9887969
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/4-amino-5-(4-methylphenyl)-7-(tert-b...,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Genistein,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins pp60(c-src),
http://linkedlifedata.com/resource/pubmed/chemical/Pyrazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrphostins,
http://linkedlifedata.com/resource/pubmed/chemical/src-Family Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/tyrphostin A23
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0007-1188
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
129
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1347-54
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:10742290-Animals,
pubmed-meshheading:10742290-Arteries,
pubmed-meshheading:10742290-Calcium Channels,
pubmed-meshheading:10742290-Dose-Response Relationship, Drug,
pubmed-meshheading:10742290-Ear,
pubmed-meshheading:10742290-Electric Stimulation,
pubmed-meshheading:10742290-Enzyme Inhibitors,
pubmed-meshheading:10742290-Genistein,
pubmed-meshheading:10742290-Membrane Potentials,
pubmed-meshheading:10742290-Muscle, Smooth, Vascular,
pubmed-meshheading:10742290-Protein-Tyrosine Kinases,
pubmed-meshheading:10742290-Proto-Oncogene Proteins pp60(c-src),
pubmed-meshheading:10742290-Pyrazoles,
pubmed-meshheading:10742290-Pyrimidines,
pubmed-meshheading:10742290-Rabbits,
pubmed-meshheading:10742290-Tyrphostins,
pubmed-meshheading:10742290-src-Family Kinases
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pubmed:year |
2000
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pubmed:articleTitle |
Effects of protein tyrosine kinase inhibitors on voltage-operated calcium channel currents in vascular smooth muscle cells and pp60(c-src) kinase activity.
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pubmed:affiliation |
Imperial College School of Medicine, National Heart & Lung Institute, St Mary's Hospital, London W2 1NY, UK. v.wijetunge@ic.ac.uk
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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