Source:http://linkedlifedata.com/resource/pubmed/id/17181555
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2007-2-1
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pubmed:abstractText |
Neuronal nicotinic acetylcholine receptors (nAChRs) are ligand-gated cation channels that can modulate various neuronal processes by altering intracellular Ca(2+) levels. Following nAChR stimulation Ca(2+) can enter cells either directly, through the intrinsic ion channel, or indirectly following voltage-operated Ca(2+) channel (VOCC) activation; Ca(2+) levels can subsequently be amplified via Ca(2+)-induced Ca(2+) release from intracellular stores. We have used subtype-selective nAChR agonists to investigate the Ca(2+) sources contributing to alpha7 and non-alpha7 nAChR-mediated increases in intracellular Ca(2+) in PC12 cells. Application of the alpha7 nAChR positive allosteric modulator PNU 120596 (10 mum), in conjunction with the alpha7 nAChR agonist, compound A [(R)-N-(1-azabicyclo[2.2.2]oct-3-yl)(5-(2-pyridyl)thiophene-2-carboxamide), 10 nm], produces a rapid increase in fluo-3 fluorescence that is prevented by the selective alpha7 nAChR antagonist alpha-bungarotoxin. The non-alpha7 nAChR agonist 5-Iodo-A-85380 produces alpha-bungarotoxin-insensitive increases in intracellular Ca(2+) (EC(50) = 11.2 mum). Using these selective agonists or KCl in conjunction with general and selective VOCC inhibitors, we demonstrate that the primary route of Ca(2+) entry following either non-alpha7 nAChR activation or KCl stimulation is via L-type VOCCs. In contrast, the alpha7 nAChR-mediated response is unaffected by VOCC blockers but is inhibited by modulators of intracellular Ca(2+) stores. These results indicate that alpha7 and non-alpha7 nAChRs are differentially coupled to Ca(2+)-induced Ca(2+) release and VOCCs, respectively.
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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/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channel Blockers,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Cholinergic Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Cholinergic Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Chloride,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Nicotinic,
http://linkedlifedata.com/resource/pubmed/chemical/Ryanodine,
http://linkedlifedata.com/resource/pubmed/chemical/alpha7 nicotinic acetylcholine...
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0022-3042
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
100
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1089-96
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pubmed:dateRevised |
2010-6-4
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pubmed:meshHeading |
pubmed-meshheading:17181555-Animals,
pubmed-meshheading:17181555-Calcium,
pubmed-meshheading:17181555-Calcium Channel Blockers,
pubmed-meshheading:17181555-Calcium Channels,
pubmed-meshheading:17181555-Calcium Signaling,
pubmed-meshheading:17181555-Cholinergic Agonists,
pubmed-meshheading:17181555-Cholinergic Antagonists,
pubmed-meshheading:17181555-Dose-Response Relationship, Drug,
pubmed-meshheading:17181555-Drug Interactions,
pubmed-meshheading:17181555-Extracellular Fluid,
pubmed-meshheading:17181555-Models, Biological,
pubmed-meshheading:17181555-PC12 Cells,
pubmed-meshheading:17181555-Potassium Chloride,
pubmed-meshheading:17181555-Radioligand Assay,
pubmed-meshheading:17181555-Rats,
pubmed-meshheading:17181555-Receptors, Nicotinic,
pubmed-meshheading:17181555-Ryanodine
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pubmed:year |
2007
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pubmed:articleTitle |
Differential coupling of alpha7 and non-alpha7 nicotinic acetylcholine receptors to calcium-induced calcium release and voltage-operated calcium channels in PC12 cells.
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pubmed:affiliation |
Department of Biology & Biochemistry, University of Bath, Bath, UK.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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