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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2007-9-20
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pubmed:abstractText |
The marine toxin gambierol, a polyether ladder toxin derived from the marine dinoflagellate Gambierdiscus toxicus, was evaluated for interaction with voltage-gated sodium channels (VGSCs) in cerebellar granule neuron (CGN) cultures. At concentrations ranging from 10 nM to 10 microM, gambierol alone had no effect on the intracellular Ca2+ concentration [Ca2+]i of exposed CGN cultures. Furthermore, there was no evidence of neurotoxicity in CGN cultures exposed for 2 h to gambierol (1 nM-10 microM). However, gambierol was a potent inhibitor (IC50 = 189 nM) of the elevation of [Ca2+]i that accompanies exposure of CGN cultures to the VGSC activator brevetoxin-2 (PbTx-2). To further explore the potential interaction of gambierol with VGSCs, the influence of gambierol on PbTx-2-induced neurotoxicity was assessed. Gambierol reduced the PbTx-2-induced efflux of lactate dehydrogenase in exposed CGN cultures in a concentration-dependent manner (IC50 = 471 nM). It is noteworthy that the potencies of gambierol as an inhibitor of both PbTx-2-induced Ca2+ influx and cytotoxicity were coincident. Finally, the inhibitory effects of gambierol on PbTx-2-induced elevation of [Ca2+]i were compared with those of brevenal, a natural inhibitor of the toxic effects of brevetoxin isolated from cultures of Karina brevis. Like gambierol, brevenal inhibited PbTx-2-induced elevation of [Ca2+]i in a concentration-dependent manner (IC50 = 108.6 nM). These results provide evidence for gambierol acting as a functional antagonist of neurotoxin site 5 on neuronal VGSCs.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/17609421-10737600,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17609421-10936626,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17609421-11086218,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17609421-11895121,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17609421-12169106,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17609421-12182604,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17609421-12657316,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17609421-12852956,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17609421-1324537,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17609421-14505411,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17609421-14757203,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17609421-14907713,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17609421-15233378,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17609421-15372697,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17609421-15447946,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17609421-15679307,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17609421-15689421,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17609421-15808523,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17609421-15866774,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17609421-16307526,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17609421-16791001,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17609421-16868017,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17609421-2426567,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17609421-2884353,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17609421-7296283,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17609421-9029269,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17609421-9383457,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17609421-9454792,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17609421-9756332,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17609421-9920485
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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/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Ciguatoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Ethers, Cyclic,
http://linkedlifedata.com/resource/pubmed/chemical/Marine Toxins,
http://linkedlifedata.com/resource/pubmed/chemical/Oxocins,
http://linkedlifedata.com/resource/pubmed/chemical/Polycyclic Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Ptychodiscus brevis T2 toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium Channel Blockers,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/gambierol
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0022-3565
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
323
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
174-9
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:17609421-Animals,
pubmed-meshheading:17609421-Animals, Newborn,
pubmed-meshheading:17609421-Binding Sites,
pubmed-meshheading:17609421-Calcium,
pubmed-meshheading:17609421-Cell Survival,
pubmed-meshheading:17609421-Cells, Cultured,
pubmed-meshheading:17609421-Cerebellum,
pubmed-meshheading:17609421-Ciguatoxins,
pubmed-meshheading:17609421-Ethers, Cyclic,
pubmed-meshheading:17609421-Marine Toxins,
pubmed-meshheading:17609421-Molecular Structure,
pubmed-meshheading:17609421-Neurons,
pubmed-meshheading:17609421-Oxocins,
pubmed-meshheading:17609421-Polycyclic Compounds,
pubmed-meshheading:17609421-Rats,
pubmed-meshheading:17609421-Rats, Sprague-Dawley,
pubmed-meshheading:17609421-Sodium Channel Blockers,
pubmed-meshheading:17609421-Sodium Channels,
pubmed-meshheading:17609421-Synaptosomes
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pubmed:year |
2007
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pubmed:articleTitle |
Gambierol acts as a functional antagonist of neurotoxin site 5 on voltage-gated sodium channels in cerebellar granule neurons.
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pubmed:affiliation |
Department of Biology, Xavier University of Louisiana, New Orleans, Louisiana, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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