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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1990-8-21
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pubmed:abstractText |
The contribution of polyphosphoinositides to muscarinic receptor-stimulated phosphoinositide turnover has been evaluated for intact and digitonin-permeabilized human SK-N-SH neuroblastoma cells. Addition of carbamoylcholine to [3H]inositol-prelabeled intact cells resulted in a rapid (5-10 sec) loss of phosphatidylinositol-4,5-bisphosphate and the concomitant appearance of radiolabeled inositol-1,4,5-trisphosphate, inositol-1,3,4-trisphosphate, and inositol tetrakisphosphate. In the presence of the agonist, production of these inositol polyphosphates remained enhanced for up to 45 min. Inositol mono- and bisphosphates steadily accumulated in response to receptor activation and in the presence of Li+ comprised greater than 95% of agonist-stimulated inositol phosphate formation at incubation times greater than 5 min. The major inositol bisphosphate isomer was the 1,4-species. Of the two inositol monophosphates produced, radioactivity recovered in inositol-4-monophosphate increased continuously, whereas that in the inositol-1-monophosphate/inositol-3-monophosphate fraction was delayed in appearance but thereafter progressively accumulated. Omission of Ca2+ reduced carbamoylcholine-stimulated inositol phosphate release by greater than 50% but did not significantly influence the ratio of inositol monophosphates formed. Upon addition of atropine to agonist-pretreated cells, radioactivity was lost from inositol phosphates in the following order: inositol-1,4,5-trisphosphate greater than inositol-1,3,4-trisphosphate greater than inositol-1,4-bisphosphate = inositol-4-monophosphate greater than inositol-1-monophosphate/inositol-3-monophosphate. Although carbamoylcholine addition to digitonin-permeabilized cells also resulted in a sustained release of inositol monophosphates, relatively more inositol-4-monophosphate was produced in these preparations. Omission of ATP from permeabilized cell incubations inhibited carbamoylcholine-stimulated 'inositol phosphate formation by greater than 70%. Whole homogenates of SK-N-SH cells metabolized added inositol-1,4,5-trisphosphate and inositol-1,4-bisphosphate exclusively to inositol-4-monophosphate, whereas inositol-1,3,4,5-tetrakisphosphate was degraded to inositol-1- or 3-monophosphate. Measurement of inositol trisphosphate 3'-kinase and 5'-phosphatase activities revealed that, following permeabilization, 3'-kinase activity was diminished, whereas that of 5'-phosphatase was enhanced. The results indicate that occupancy of muscarinic cholinergic receptors in SK-N-SH cells elicits a continuous Ca2(+)-dependent breakdown of the polyphosphoinositides rather than of phosphatidylinositol.(ABSTRACT TRUNCATED AT 400 WORDS)
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Carbachol,
http://linkedlifedata.com/resource/pubmed/chemical/Digitonin,
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/Phosphatidylinositol Phosphates,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositols,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoric Monoester Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotransferases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotransferases (Alcohol Group...,
http://linkedlifedata.com/resource/pubmed/chemical/inositol triphosphate...
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0026-895X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
38
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
54-63
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:2164631-Calcium,
pubmed-meshheading:2164631-Carbachol,
pubmed-meshheading:2164631-Digitonin,
pubmed-meshheading:2164631-Humans,
pubmed-meshheading:2164631-Inositol Phosphates,
pubmed-meshheading:2164631-Kinetics,
pubmed-meshheading:2164631-Neuroblastoma,
pubmed-meshheading:2164631-Phosphatidylinositol Phosphates,
pubmed-meshheading:2164631-Phosphatidylinositols,
pubmed-meshheading:2164631-Phosphoric Monoester Hydrolases,
pubmed-meshheading:2164631-Phosphotransferases,
pubmed-meshheading:2164631-Phosphotransferases (Alcohol Group Acceptor),
pubmed-meshheading:2164631-Tumor Cells, Cultured
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pubmed:year |
1990
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pubmed:articleTitle |
Polyphosphoinositides are the major source of inositol phosphates in carbamoylcholine-stimulated SK-N-SH neuroblastoma cells.
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pubmed:affiliation |
Neuroscience Laboratory, University of Michigan, Ann Arbor 48104.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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