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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
1997-10-2
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| pubmed:abstractText |
The regulation of phosphoinositide hydrolysis by the type 1alpha metabotropic glutamate receptor (mGluR1alpha) was investigated in stably transfected baby hamster kidney (BHK) cells. Incubation of the cells with L-glutamate, quisqualate, and 1-aminocyclopentane-1S, 3R-dicarboxylic acid resulted in a marked accumulation of [3H]inositol monophosphate (InsP1) and inositol-1,4,5-trisphosphate [Ins(1,4,5)P3] mass in a time- and concentration-dependent manner. Pretreatment of BHK-mGluR1alpha cells with pertussis toxin [ 100 ng/ml, 24 hr] led to a dramatic 12-16-fold increase in the accumulation of [3H]InsP1 and a 2-fold increase in Ins(1,4,5)P3 in the absence of added agonist. Although only very low levels (</=1 microM) of L-glutamate could be detected in medium taken from control and PTX-treated cell monolayers, the PTX-elicited effect on basal [3H]InsP1 was fully reversed by preincubation of cells in the presence of glutamic-pyruvic transaminase and pyruvate, suggesting that an increased sensitivity to endogenous glutamate was responsible for the apparent agonist-independent activation of phosphoinositidase C (PIC) after PTX treatment. Consistent with this hypothesis, in the presence of glutamic-pyruvic transaminase/pyruvate, the maximal [3H]InsP1 response to quisqualate was increased by >/=75%, and the EC50 shifted leftward by 65-fold [-log EC50 values (molar), 7.26 +/- 0.23 versus 5.45 +/- 0.07; n = 4) in PTX-treated compared with control cells. In contrast, antagonist effects on agonist-stimulated [3H]InsP1 responses were similar in control and PTX-treated BHK-mGluR1alpha cells. These changes in the concentration-effect curves for mGluR agonists are consistent with a model in which the receptor associates with PTX-sensitive inhibitory (Gi/o) and PTX-insensitive stimulatory (Gq/11) G proteins that can each influence PIC activity. The present observations are consistent with a dual regulation of mGluR1alpha-mediated PIC activity that could be fundamental in controlling the output of phosphoinositide-derived messengers.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Inositol 1,4,5-Trisphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Inositol Phosphates,
http://linkedlifedata.com/resource/pubmed/chemical/Pertussis Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositols,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoric Diester Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Metabotropic Glutamate,
http://linkedlifedata.com/resource/pubmed/chemical/Tritium,
http://linkedlifedata.com/resource/pubmed/chemical/Virulence Factors, Bordetella,
http://linkedlifedata.com/resource/pubmed/chemical/glycerophosphoinositol...,
http://linkedlifedata.com/resource/pubmed/chemical/inositol 1-phosphate
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
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| pubmed:issn |
0026-895X
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
52
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
406-14
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:9281602-Amino Acid Sequence,
pubmed-meshheading:9281602-Animals,
pubmed-meshheading:9281602-Cricetinae,
pubmed-meshheading:9281602-Excitatory Amino Acid Agonists,
pubmed-meshheading:9281602-Excitatory Amino Acid Antagonists,
pubmed-meshheading:9281602-GTP-Binding Proteins,
pubmed-meshheading:9281602-Glutamic Acid,
pubmed-meshheading:9281602-Inositol 1,4,5-Trisphosphate,
pubmed-meshheading:9281602-Inositol Phosphates,
pubmed-meshheading:9281602-Kidney,
pubmed-meshheading:9281602-Kinetics,
pubmed-meshheading:9281602-Molecular Sequence Data,
pubmed-meshheading:9281602-Pertussis Toxin,
pubmed-meshheading:9281602-Phosphatidylinositols,
pubmed-meshheading:9281602-Phosphoric Diester Hydrolases,
pubmed-meshheading:9281602-Receptors, Metabotropic Glutamate,
pubmed-meshheading:9281602-Signal Transduction,
pubmed-meshheading:9281602-Stimulation, Chemical,
pubmed-meshheading:9281602-Tritium,
pubmed-meshheading:9281602-Tumor Cells, Cultured,
pubmed-meshheading:9281602-Virulence Factors, Bordetella
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| pubmed:year |
1997
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| pubmed:articleTitle |
Enhanced type 1alpha metabotropic glutamate receptor-stimulated phosphoinositide signaling after pertussis toxin treatment.
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| pubmed:affiliation |
Department of Cell Physiology and Pharmacology, University of Leicester, University Road, Leicester LE1 9HN, UK.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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