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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
1996-11-6
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pubmed:abstractText |
Capsaicin activates a non-specific cation conductance in mammalian sensory neurones. If capsaicin is applied continuously or repeatedly then there is a progressive decline in responsiveness. We have studied the mechanism of this desensitization using electrophysiological methods in cultured dorsal root ganglion neurones from adult rats. The rate of desensitization of capsaicin-induced responses is partly dependent on the extracellular calcium concentration and is slower when extracellular calcium is reduced. Desensitization is strongly inhibited by intracellular application of the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N, N, N',N'-tetraacetic acid (BAPTA). These data suggest that desensitization is due to a rapid rise in intracellular calcium levels which occurs when capsaicin-sensitive ion channels are activated. Desensitization is not reduced by the non-specific protein kinase inhibitors H7 or staurosporine or by okadaic acid, a selective inhibitor of protein phosphatases 1 and 2A. Desensitization is greatly reduced by cyclosporin A complexed to cyclophilin, which is a specific inhibitor of protein phoshatase 2B (calcineurin). A mechanism for desensitization of capsaicin responsiveness is proposed whereby the evoked rise in calcium activates calcineurin leading to dephosphorylation and desensitization of the capsaicin-sensitive ion channels.
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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/1,2-bis(2-aminophenoxy)ethane-N,N,N'...,
http://linkedlifedata.com/resource/pubmed/chemical/1-(5-Isoquinolinesulfonyl)-2-Methylp...,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Calcineurin,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calmodulin-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Capsaicin,
http://linkedlifedata.com/resource/pubmed/chemical/Chelating Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclosporine,
http://linkedlifedata.com/resource/pubmed/chemical/Egtazic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Ion Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoprotein Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0031-6768
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
431
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
828-37
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:8927498-1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine,
pubmed-meshheading:8927498-Adenosine Triphosphate,
pubmed-meshheading:8927498-Animals,
pubmed-meshheading:8927498-Calcineurin,
pubmed-meshheading:8927498-Calcium,
pubmed-meshheading:8927498-Calmodulin-Binding Proteins,
pubmed-meshheading:8927498-Capsaicin,
pubmed-meshheading:8927498-Cells, Cultured,
pubmed-meshheading:8927498-Chelating Agents,
pubmed-meshheading:8927498-Cyclosporine,
pubmed-meshheading:8927498-Drug Resistance,
pubmed-meshheading:8927498-Egtazic Acid,
pubmed-meshheading:8927498-Enzyme Inhibitors,
pubmed-meshheading:8927498-Evoked Potentials,
pubmed-meshheading:8927498-Ganglia, Spinal,
pubmed-meshheading:8927498-Ion Channel Gating,
pubmed-meshheading:8927498-Ion Channels,
pubmed-meshheading:8927498-Ligands,
pubmed-meshheading:8927498-Phosphoprotein Phosphatases,
pubmed-meshheading:8927498-Phosphorylation,
pubmed-meshheading:8927498-Protein Kinase Inhibitors,
pubmed-meshheading:8927498-Rats
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pubmed:year |
1996
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pubmed:articleTitle |
Inhibition of calcineurin inhibits the desensitization of capsaicin-evoked currents in cultured dorsal root ganglion neurones from adult rats.
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pubmed:affiliation |
Sandoz Institute for Medical Research, 5 Gower Pl, London WC1E 6BN, UK.
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pubmed:publicationType |
Journal Article
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