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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1992-3-27
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pubmed:abstractText |
In various species, including humans, 5-hydroxytryptamine (5-HT) has been shown to exert positive chronotropic and inotropic cardiac effects through different types of receptors. The goal of the present study was to investigate the regulation by 5-HT of voltage-gated Ca2+ channels in human atrial myocytes and to characterize the receptor involved. Cardiomyocytes isolated enzymatically and mechanically were voltage-clamped using the whole-cell configuration of the patch-clamp technique. Extracellular perfusion of 5-HT increased Ca2+ current (ICa) amplitude with a EC50 (0.1 microM) similar to that observed with isoprenaline. The effects of 5-HT were blocked by the addition of protein kinase A inhibitor in the pipette. In addition, the effects of 5-HT, isoprenaline, and intracellular cAMP on ICa were not additive. These results support the hypothesis that the inotropic effect of 5-HT in human atrial myocytes is related to an increase of ICa via an elevation of intracellular cAMP levels and stimulation of cAMP-dependent protein kinase. The effects of 5-HT were not blocked by antagonists of 5-HT1 (methiothepin), 5-HT2 (ketanserin), or 5-HT3 (ICS 205-930 at a low concentration) receptors. The benzamide derivatives renzapride and zacopride and the azabicyclobenzimidazolone derivative BIMU 8 increased ICa, but less efficiently than did 5-HT or 5-methoxytryptamine. Moreover, ICS 205-930 at high concentrations (greater than 1 microM) completely antagonized the effects of 5-HT. Thus, the pharmacology of the 5-HT receptor involved in an increase of ICa in human atrial myocytes resembles that recently described for the 5-HT4 receptor. In atrial myocytes dissociated from rat, rabbit, guinea pig, or frog, 5-HT at high concentrations had no effect on Ca2+ currents, suggesting that the distribution of 5-HT4 receptors in cardiac tissues is species dependent.
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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 Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Cardiotonic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0026-895X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
41
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
346-51
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:1311410-Animals,
pubmed-meshheading:1311410-Anura,
pubmed-meshheading:1311410-Atrial Function,
pubmed-meshheading:1311410-Calcium,
pubmed-meshheading:1311410-Calcium Channels,
pubmed-meshheading:1311410-Cardiotonic Agents,
pubmed-meshheading:1311410-Cells, Cultured,
pubmed-meshheading:1311410-Cyclic AMP,
pubmed-meshheading:1311410-Guinea Pigs,
pubmed-meshheading:1311410-Heart,
pubmed-meshheading:1311410-Heart Atria,
pubmed-meshheading:1311410-Humans,
pubmed-meshheading:1311410-Membrane Potentials,
pubmed-meshheading:1311410-Myocardium,
pubmed-meshheading:1311410-Rabbits,
pubmed-meshheading:1311410-Rats,
pubmed-meshheading:1311410-Receptors, Serotonin,
pubmed-meshheading:1311410-Serotonin,
pubmed-meshheading:1311410-Species Specificity
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pubmed:year |
1992
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pubmed:articleTitle |
Serotonin increases calcium current in human atrial myocytes via the newly described 5-hydroxytryptamine4 receptors.
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pubmed:affiliation |
CRBM, CNRS UPR 8402/INSERM U 249, Montpellier, France.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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