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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
1998-6-18
|
| pubmed:databankReference | |
| pubmed:abstractText |
Prolonged stimulation of rat A7r5 aortic smooth muscle cells with 3 microM vasopressin, or of hamster DDT1 MF-2 smooth muscle cells with 10 microM bradykinin or 100 microM histamine led within 4 h to a 40-50% down-regulation of the type 1 InsP3 receptor (InsP3R-1) and of the type 3 InsP3 receptor (InsP3R-3). InsP3R down-regulation was a cell- and agonist-specific process, since several other agonists acting on PLC-coupled receptors did not change the expression level of the InsP3R isoforms in these cell types and since no agonist-induced down-regulation of InsP3Rs was observed in HeLa cells. Down-regulation of InsP3Rs was prevented by an inhibitor of proteasomal protease activity, N-acetyl-Leu-Leu-norleucinal (ALLN). The Ca2+ channel blocker verapamil (2 microM) also induced InsP3R-1 down-regulation (43%) in A7r5 cells, which was inhibited by ALLN. In A7r5 cells transiently transfected with a cDNA construct, bearing a luciferase coding sequence under control of the rat InsP3R-1 promoter, reduced luciferase activity could be demonstrated upon stimulation of cells with vasopressin or verapamil. Thus, besides enhanced protein degradation, a reduction of InsP3R promoter activity might contribute to the down-regulation of InsP3Rs in A7r5 cells. We next investigated the effect of InsP3R down-regulation on Ca2+ responses in A7r5 cells. A rightward shift in the dose-response curve for InsP3-induced Ca2+ release was observed in permeabilized monolayers of vasopressin-pretreated A7r5 cells (EC50 630 nM and 400 nM for pretreated and non-pretreated cells, respectively). The Ca2+ responses to threshold doses of vasopressin were markedly reduced in intact vasopressin-pretreated cells. We conclude that prolonged agonist-exposure leads to down-regulation of InsP3Rs in A7r5 and DDT, MF-2 smooth muscle cells. The mechanism of down-regulation likely involves proteasomal degradation and reduction of InsP3R promoter activity. Moreover, down-regulation of InsP3Rs resulted in desensitization of Ca2+ release from InsP3 sensitive stores.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Bradykinin,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channel Blockers,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Carbachol,
http://linkedlifedata.com/resource/pubmed/chemical/Histamine,
http://linkedlifedata.com/resource/pubmed/chemical/ITPR1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Inositol 1,4,5-Trisphosphate...,
http://linkedlifedata.com/resource/pubmed/chemical/Parasympathomimetics,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Vasopressins,
http://linkedlifedata.com/resource/pubmed/chemical/Verapamil
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jan
|
| pubmed:issn |
0143-4160
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
23
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
11-21
|
| pubmed:dateRevised |
2008-11-21
|
| pubmed:meshHeading |
pubmed-meshheading:9570006-Adenosine Triphosphate,
pubmed-meshheading:9570006-Animals,
pubmed-meshheading:9570006-Aorta,
pubmed-meshheading:9570006-Bradykinin,
pubmed-meshheading:9570006-Calcium,
pubmed-meshheading:9570006-Calcium Channel Blockers,
pubmed-meshheading:9570006-Calcium Channels,
pubmed-meshheading:9570006-Carbachol,
pubmed-meshheading:9570006-Cricetinae,
pubmed-meshheading:9570006-Down-Regulation,
pubmed-meshheading:9570006-Gene Expression,
pubmed-meshheading:9570006-Genes, Reporter,
pubmed-meshheading:9570006-HeLa Cells,
pubmed-meshheading:9570006-Histamine,
pubmed-meshheading:9570006-Humans,
pubmed-meshheading:9570006-Inositol 1,4,5-Trisphosphate Receptors,
pubmed-meshheading:9570006-Muscle, Smooth, Vascular,
pubmed-meshheading:9570006-Parasympathomimetics,
pubmed-meshheading:9570006-Promoter Regions, Genetic,
pubmed-meshheading:9570006-Rats,
pubmed-meshheading:9570006-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:9570006-Transfection,
pubmed-meshheading:9570006-Vasopressins,
pubmed-meshheading:9570006-Verapamil
|
| pubmed:year |
1998
|
| pubmed:articleTitle |
Agonist-induced down-regulation of type 1 and type 3 inositol 1,4,5-trisphosphate receptors in A7r5 and DDT1 MF-2 smooth muscle cells.
|
| pubmed:affiliation |
Laboratorium voor Fysiologie, Campus Gasthuisberg O/N, KU Leuven, Belgium.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|