Source:http://linkedlifedata.com/resource/pubmed/id/10087139
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
1999-6-4
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pubmed:abstractText |
The effects of extracellular adenosine 5'-triphosphate (ATP) on the delayed rectifier K+ current (IK) were studied in guinea-pig ventricular myocytes using the whole-cell voltage-clamp technique. ATP increased IK concentration dependently with a concentration eliciting a half-maximal response of 1.86 microM and a maximal increase of about 1.8-fold. The enhancement of IK developed slowly, the effect reaching a maximum in about 1.6 min after application of ATP. The rank order of agonist potency in enhancing IK was 2-methylthio-ATP>/= ATP>>alpha,beta-methylene-ATP. The ATP response was attenuated in guanosine 5'-O-(2-thiodiphosphate) (GDPbetaS)- loaded cells, but was not affected by pertussis toxin (PTX)-pre-treatment, indicating that a PTX-insensitive G protein is involved in the response. These features are consistent with operation of P2Y-type purinoceptors. ATP produced a further increase in IK stimulated maximally either by isoprenaline (1 microM) through protein kinase A (PKA) or by 12-O-tetradecanoylphorbol 13-acetate (TPA, 100 nM) through protein kinase C (PKC), while 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7, 10 microM) did not affect the ATP response, suggesting that PKA and PKC do not mediate the response. ATP irreversibly enhanced IK in cells loaded with adenosine 5'-O-(3-thiotriphosphate) (ATPgammaS, 5 mM) or okadaic acid (10 microM), a phosphatase inhibitor, suggesting that a phosphorylation step is present after the receptor stimulation. Genistein, an inhibitor of tyrosine phosphorylation, suppressed the ATP response significantly, while daidzein, an inactive analogue of genistein, had little effect on it, although both genistein or daidzein alone decreased IK. It is hypothesized that tyrosine phosphorylation plays a role in the signalling pathway involved in the enhancement of cardiac IK by P2Y-purinergic stimulation.
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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/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Delayed Rectifier Potassium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Pertussis Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels, Voltage-Gated,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Purinergic P2,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/Virulence Factors, Bordetella
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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 | |
pubmed:issnType |
Print
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pubmed:volume |
437
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
635-42
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:10087139-Adenosine Triphosphate,
pubmed-meshheading:10087139-Animals,
pubmed-meshheading:10087139-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:10087139-Delayed Rectifier Potassium Channels,
pubmed-meshheading:10087139-Electric Stimulation,
pubmed-meshheading:10087139-Electrophysiology,
pubmed-meshheading:10087139-Extracellular Space,
pubmed-meshheading:10087139-GTP-Binding Proteins,
pubmed-meshheading:10087139-Guinea Pigs,
pubmed-meshheading:10087139-Heart,
pubmed-meshheading:10087139-Heart Ventricles,
pubmed-meshheading:10087139-Membrane Potentials,
pubmed-meshheading:10087139-Myocardium,
pubmed-meshheading:10087139-Patch-Clamp Techniques,
pubmed-meshheading:10087139-Pertussis Toxin,
pubmed-meshheading:10087139-Phosphorylation,
pubmed-meshheading:10087139-Potassium Channels,
pubmed-meshheading:10087139-Potassium Channels, Voltage-Gated,
pubmed-meshheading:10087139-Protein Kinase C,
pubmed-meshheading:10087139-Receptors, Purinergic P2,
pubmed-meshheading:10087139-Tyrosine,
pubmed-meshheading:10087139-Ventricular Function,
pubmed-meshheading:10087139-Virulence Factors, Bordetella
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pubmed:year |
1999
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pubmed:articleTitle |
On the mechanism of the enhancement of delayed rectifier K+ current by extracellular ATP in guinea-pig ventricular myocytes.
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pubmed:affiliation |
Department of Physiology, Saga Medical School, Saga 849-8501, Japan. matsubat@smsnet.saga-med.ac.jp
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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