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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
1994-4-18
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pubmed:abstractText |
Stimulation of SH-SY5Y human neuroblastoma cells with carbachol, a muscarinic agonist, down-regulates the type I inositol 1,4,5-trisphosphate (InsP3) receptor by > 90% with maximal and half-maximal effects after approximately 6 h and approximately 1 h, respectively. Examination of the mechanistic basis of this down-regulation revealed that carbachol increased the rate of type I InsP3 receptor degradation (radiolabeled immunoprecipitable receptor was lost from cells with half-times of > 8 h and approximately 1 h in the absence and presence of carbachol, respectively) and that the concentration of type I InsP3 receptor mRNA, despite a transient decrease after 3 h, did not correlate with levels of the receptor. Only those muscarinic receptor subtypes coupled to stimulation of phosphoinositide hydrolysis were capable of causing type I InsP3 receptor down-regulation. Ca2+ mobilization was pivotal to the mechanisms of receptor down-regulation, since perturbation of Ca2+ homeostasis with either EGTA or thapsigargin blocked the ability of carbachol to accelerate receptor degradation. Studies with thapsigargin also revealed that both functional InsP3-sensitive Ca2+ stores and persistent elevation of InsP3 concentration were required for down-regulation to occur. In conclusion, phosphoinositidase C-linked muscarinic receptors down-regulate the type I InsP3 receptor by accelerating its degradation. It appears that this process is initiated by persistent discharge of intracellular Ca2+ stores via the channels formed by tetramerically complexed type I InsP3 receptors.
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pubmed:grant |
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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/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Transporting ATPases,
http://linkedlifedata.com/resource/pubmed/chemical/Carbachol,
http://linkedlifedata.com/resource/pubmed/chemical/Egtazic Acid,
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/Inositol 1,4,5-Trisphosphate...,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositols,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Muscarinic,
http://linkedlifedata.com/resource/pubmed/chemical/Terpenes,
http://linkedlifedata.com/resource/pubmed/chemical/Thapsigargin
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
18
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pubmed:volume |
269
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7963-9
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:8132516-Animals,
pubmed-meshheading:8132516-CHO Cells,
pubmed-meshheading:8132516-Calcium,
pubmed-meshheading:8132516-Calcium Channels,
pubmed-meshheading:8132516-Calcium-Transporting ATPases,
pubmed-meshheading:8132516-Carbachol,
pubmed-meshheading:8132516-Cell Line,
pubmed-meshheading:8132516-Cricetinae,
pubmed-meshheading:8132516-Down-Regulation,
pubmed-meshheading:8132516-Egtazic Acid,
pubmed-meshheading:8132516-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:8132516-Gene Expression,
pubmed-meshheading:8132516-Humans,
pubmed-meshheading:8132516-Inositol 1,4,5-Trisphosphate,
pubmed-meshheading:8132516-Inositol 1,4,5-Trisphosphate Receptors,
pubmed-meshheading:8132516-Kinetics,
pubmed-meshheading:8132516-Neuroblastoma,
pubmed-meshheading:8132516-Phosphatidylinositols,
pubmed-meshheading:8132516-Phosphorylation,
pubmed-meshheading:8132516-RNA, Messenger,
pubmed-meshheading:8132516-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:8132516-Receptors, Muscarinic,
pubmed-meshheading:8132516-Terpenes,
pubmed-meshheading:8132516-Thapsigargin,
pubmed-meshheading:8132516-Transfection,
pubmed-meshheading:8132516-Tumor Cells, Cultured
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pubmed:year |
1994
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pubmed:articleTitle |
Muscarinic receptor activation down-regulates the type I inositol 1,4,5-trisphosphate receptor by accelerating its degradation.
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pubmed:affiliation |
Department of Cell Physiology and Pharmacology, University of Leicester.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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