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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions |
umls-concept:C0021547,
umls-concept:C0026844,
umls-concept:C0030685,
umls-concept:C0043167,
umls-concept:C0086376,
umls-concept:C0300926,
umls-concept:C0332120,
umls-concept:C0391871,
umls-concept:C0439834,
umls-concept:C0596235,
umls-concept:C0680255,
umls-concept:C1283071,
umls-concept:C1314939,
umls-concept:C1963578
|
| pubmed:issue |
11
|
| pubmed:dateCreated |
1992-5-12
|
| pubmed:abstractText |
The role of pertussis toxin (PT)-sensitive and -insensitive guanine nucleotide-binding proteins (G proteins) in the stimulation of Ca2+ mobilization by thrombin was investigated in cultured rat aortic smooth muscle cells. Characterization using immunoblotting with specific antisera indicated the presence in isolated membranes of the G alpha i2, G alpha i3, G alpha s, G beta 35, and G beta 36 protein subunits as well as a lower molecular weight species of unknown identity. To assess the importance of G proteins in the coupling of thrombin receptors to Ca2+ mobilization, we investigated the effect of PT on Ca2+ responses using fluorescence spectroscopy and the Ca2+ indicator dye Fura-2. Pretreatment of cells for 2 h with PT (1 microgram/ml), which produced 91.3% ADP-ribosylation of PT-sensitive G proteins, did not affect the magnitude of thrombin-induced release of Ca2+ from internal stores, suggesting that the residual 8.7% of PT-sensitive G proteins, or PT-insensitive mechanisms, was responsible for Ca2+ release. However, after an 18-h pretreatment with PT, which produced ADP-ribosylation of the total complement of PT-sensitive G proteins, the thrombin-induced peak Ca2+ response was inhibited by approximately 72%, suggesting that the major fraction of the Ca2+ response was mediated by a slowly ribosylating component. The delayed effect of the toxin was not caused by down-regulation of the beta-subunit of G proteins because quantitative immunoblots showed that levels of the beta-subunit remained constant throughout the period of PT pretreatment. It was also not caused by a reduction in the size of the thrombin-releasable Ca2+ pool because Ca2+ release induced by agents that release Ca2+ directly from internal stores, 2,5-di-tert-butylhydroquinone or thapsigargin, was not affected. In addition, the delayed effect of PT could not be explained in terms of differences in thrombin-induced [3H]inositol trisphosphate (IP3) formation because the level of inhibition of IP3 formation after a 2-h PT treatment was similar to that present after an 18-h pretreatment. The results indicate that a slowly ribosylating PT-sensitive species is the major G protein pathway that couples thrombin-receptor activation to Ca2+ mobilization. This G protein appears to be involved not in the mechanisms that generate IP3 but rather possibly in coupling at the level of the intracellular Ca2+ store.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2,5-di-tert-butylhydroquinone,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Diphosphate Ribose,
http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Egtazic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroquinones,
http://linkedlifedata.com/resource/pubmed/chemical/Inositol 1,4,5-Trisphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Lanthanum,
http://linkedlifedata.com/resource/pubmed/chemical/Pertussis Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Terpenes,
http://linkedlifedata.com/resource/pubmed/chemical/Thapsigargin,
http://linkedlifedata.com/resource/pubmed/chemical/Thrombin,
http://linkedlifedata.com/resource/pubmed/chemical/Virulence Factors, Bordetella
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Apr
|
| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
15
|
| pubmed:volume |
267
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
7295-302
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:1559973-Adenosine Diphosphate Ribose,
pubmed-meshheading:1559973-Animals,
pubmed-meshheading:1559973-Antioxidants,
pubmed-meshheading:1559973-Autoradiography,
pubmed-meshheading:1559973-Blotting, Western,
pubmed-meshheading:1559973-Calcium,
pubmed-meshheading:1559973-Egtazic Acid,
pubmed-meshheading:1559973-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:1559973-GTP-Binding Proteins,
pubmed-meshheading:1559973-Hydroquinones,
pubmed-meshheading:1559973-Inositol 1,4,5-Trisphosphate,
pubmed-meshheading:1559973-Lanthanum,
pubmed-meshheading:1559973-Muscle, Smooth, Vascular,
pubmed-meshheading:1559973-Pertussis Toxin,
pubmed-meshheading:1559973-Rats,
pubmed-meshheading:1559973-Terpenes,
pubmed-meshheading:1559973-Thapsigargin,
pubmed-meshheading:1559973-Thrombin,
pubmed-meshheading:1559973-Virulence Factors, Bordetella
|
| pubmed:year |
1992
|
| pubmed:articleTitle |
Thrombin-induced Ca2+ mobilization in vascular smooth muscle utilizes a slowly ribosylating pertussis toxin-sensitive G protein. Evidence for the involvement of a G protein in inositol trisphosphate-dependent Ca2+ release.
|
| pubmed:affiliation |
Baker Medical Research Institute, Alfred Hospital, Prahran, Victoria, Australia.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|