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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1999-2-11
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pubmed:abstractText |
Tetanus toxin (TeTx) is a powerful clostridial neurotoxin that inhibits Ca2+-dependent neurotransmitter secretion as do the botulinum neurotoxins (BoNTs). We found that TeTx (but not BoNT/A) produced a specific time- and dose-dependent inhibition of Na+-dependent [3H]5-hydroxytryptamine (serotonin, 5-HT) uptake in rat CNS synaptosomes. This effect was found in all CNS tryptaminergic areas, being maximal in the hippocampus and occipital cortex. TeTx produced the maximum reduction in [3H]5-HT uptake after 30 min of preincubation, being significant also at lower doses (10(-12) M) or shorter incubation times (10 min). Serotonin transport inhibitors such as fenfluramine (IC50, 11.0 +/- 0.9 microM), paroxetine (IC50, 33.5 +/- 0.1 microM), and imipramine (IC50, 89.9 +/- 5.7 microM) were 3 or 4 orders of magnitude less potent than TeTx (IC50, 8.7 +/- 1.0 nM). Of the two fragments of TeTx, (the C-terminal portion of the neurotoxin heavy chain, which is responsible for the binding to the nerve tissue) was consistently more effective than the L-H(N) fragment (the light neurotoxin chain disulfide linked to the N-terminal portion of the heavy chain, which is responsible for the toxic metalloprotease action) as inhibitor of [3H]5-HT uptake in synaptosomal preparations (56 +/- 5% and 95 +/- 3% with respect to control, respectively). Antagonism of the toxin-induced [3H]5-HT uptake blockade could not be reversed by zinc chelators but did have the ability to antagonize the TeTx inhibition of basal and K+-evoked [3H]5-HT release in rat synaptosomes. The reduction in serotonin accumulation induced by TeTx could be responsible for some tetanic symptoms that have been related to the serotonergic system.
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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/1,10-phenanthroline,
http://linkedlifedata.com/resource/pubmed/chemical/Botulinum Toxins,
http://linkedlifedata.com/resource/pubmed/chemical/Captopril,
http://linkedlifedata.com/resource/pubmed/chemical/Fenfluramine,
http://linkedlifedata.com/resource/pubmed/chemical/Imipramine,
http://linkedlifedata.com/resource/pubmed/chemical/Paroxetine,
http://linkedlifedata.com/resource/pubmed/chemical/Phenanthrolines,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Uptake Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium,
http://linkedlifedata.com/resource/pubmed/chemical/Tetanus Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Tritium
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0006-2952
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
57
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
111-20
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:9920291-Animals,
pubmed-meshheading:9920291-Biological Transport,
pubmed-meshheading:9920291-Botulinum Toxins,
pubmed-meshheading:9920291-Brain,
pubmed-meshheading:9920291-Captopril,
pubmed-meshheading:9920291-Fenfluramine,
pubmed-meshheading:9920291-Imipramine,
pubmed-meshheading:9920291-Kinetics,
pubmed-meshheading:9920291-Male,
pubmed-meshheading:9920291-Organ Specificity,
pubmed-meshheading:9920291-Paroxetine,
pubmed-meshheading:9920291-Phenanthrolines,
pubmed-meshheading:9920291-Rats,
pubmed-meshheading:9920291-Rats, Sprague-Dawley,
pubmed-meshheading:9920291-Serotonin,
pubmed-meshheading:9920291-Serotonin Uptake Inhibitors,
pubmed-meshheading:9920291-Sodium,
pubmed-meshheading:9920291-Synaptosomes,
pubmed-meshheading:9920291-Temperature,
pubmed-meshheading:9920291-Tetanus Toxin,
pubmed-meshheading:9920291-Tritium
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pubmed:year |
1999
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pubmed:articleTitle |
Inhibition by tetanus toxin of sodium-dependent, high-affinity [3H]5-hydroxytryptamine uptake in rat synaptosomes.
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pubmed:affiliation |
Department de Bioquímica i de Biologia Molecular, Facultat de Medicina, Universitat Autonoma de Barcelona, Bellaterra, Spain.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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