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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:dateCreated |
1996-12-30
|
| pubmed:abstractText |
Lithium has a biphasic effect of the agonist-dependent accumulation of Ins(1,4,5)P3 in human neuroblastoma SH-SY5Y cells. These effects consist of a transient reduction, followed by a long-lasting increase in Ins(1,4,5)P3 as compared to controls. The Li+ effects are dose dependent, and were observed at concentrations used in the treatment of bipolar disorders, and thus may have therapeutic implications. The mechanism of the Li+ effect on Ins(1,4,5)P3 accumulation requires further investigation. The transient reduction of Ins(1,4,5)P3 was observed under conditions where Li+ causes only a moderate increase in the inositol mono- and bi-phosphates. Supplementation with exogenous inositol had no effect on the level of Ins(1,4,5)P3, indicating that the mechanism of the Li(+)-dependent reduction of Ins(1,4,5)P3 is not due to inositol depletion. Li+ did not interfere with degradation of Ins(1,4,5)P3 after receptor-blockage with atropine, suggesting that Li+ has no direct effect on the Ins(1,4,5)P3 metabolizing enzymes. A direct effect of Li+ on the phospholipase C is also unlikely. Entry of Ca2+ into the cells is an important factor, which affects agonist-stimulated accumulation of Ins(1,4,5)P3, as well as absolute values of Li(+)-dependent increase in Ins(1,4,5)P3; however, it is not essential for the manifestation of Li+ effects. Our results also show that manifestation of Li+ effects in human neuroblastoma cells requires the stimulation of muscarinic receptors and activation of PLCs, PKCs, and/or that other staurosporine/H-7/GF 109203X-sensitive protein kinases are involved in the regulation of Ins(1,4,5)P3 during the plateau phase of ACh-stimulation. We also suggest an important role for these enzymes in the Li(+)-dependent elevation of Ins(1,4,5)P3.
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1-(5-Isoquinolinesulfonyl)-2-Methylp...,
http://linkedlifedata.com/resource/pubmed/chemical/Acetylcholine,
http://linkedlifedata.com/resource/pubmed/chemical/Atropine,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Egtazic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
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/Lithium,
http://linkedlifedata.com/resource/pubmed/chemical/Maleimides,
http://linkedlifedata.com/resource/pubmed/chemical/Nickel,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositols,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Staurosporine,
http://linkedlifedata.com/resource/pubmed/chemical/bisindolylmaleimide I,
http://linkedlifedata.com/resource/pubmed/chemical/nickel chloride
|
| pubmed:status |
MEDLINE
|
| pubmed:issn |
0065-2571
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
36
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
245-64
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:8869750-1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine,
pubmed-meshheading:8869750-Acetylcholine,
pubmed-meshheading:8869750-Atropine,
pubmed-meshheading:8869750-Calcium,
pubmed-meshheading:8869750-Egtazic Acid,
pubmed-meshheading:8869750-Enzyme Inhibitors,
pubmed-meshheading:8869750-Humans,
pubmed-meshheading:8869750-Indoles,
pubmed-meshheading:8869750-Inositol 1,4,5-Trisphosphate,
pubmed-meshheading:8869750-Inositol Phosphates,
pubmed-meshheading:8869750-Lithium,
pubmed-meshheading:8869750-Maleimides,
pubmed-meshheading:8869750-Neuroblastoma,
pubmed-meshheading:8869750-Nickel,
pubmed-meshheading:8869750-Phosphatidylinositols,
pubmed-meshheading:8869750-Protein Kinase Inhibitors,
pubmed-meshheading:8869750-Signal Transduction,
pubmed-meshheading:8869750-Staurosporine,
pubmed-meshheading:8869750-Tumor Cells, Cultured
|
| pubmed:year |
1996
|
| pubmed:articleTitle |
Phosphoinositide signalling in human neuroblastoma cells: biphasic effect of Li+ on the level of the inositolphosphate second messengers.
|
| pubmed:affiliation |
Department of Pharmacology, University of Wisconsin Medical School, Madison 53706, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|