Source:http://linkedlifedata.com/resource/pubmed/id/18467629
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
11
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| pubmed:dateCreated |
2008-6-6
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| pubmed:abstractText |
We examined the effect of alpha(1)-adrenoceptor subtype-specific stimulation on L-type Ca2+ current (I(Ca)) and elucidated the subtype-specific intracellular mechanisms for the regulation of L-type Ca2+ channels in isolated rat ventricular myocytes. We confirmed the protein expression of alpha(1A)- and alpha(1B)-adrenoceptor subtypes at the transverse tubules (T-tubules) and found that simultaneous stimulation of these 2 receptor subtypes by nonsubtype selective agonist, phenylephrine, showed 2 opposite effects on I(Ca) (transient decrease followed by sustained increase). However, selective alpha(1A)-adrenoceptor stimulation (> or =0.1 micromol/L A61603) only potentiated I(Ca), and selective alpha(1B)-adrenoceptor stimulation (10 mumol/L phenylephrine with 2 micromol/L WB4101) only decreased I(Ca). The positive effect by alpha(1A)-adrenoceptor stimulation was blocked by the inhibition of phospholipase C (PLC), protein kinase C (PKC), or Ca2+/calmodulin-dependent protein kinase II (CaMKII). The negative effect by alpha(1B)-adrenoceptor stimulation disappeared after the treatment of pertussis toxin or by the prepulse depolarization, but was not attributable to the inhibition of cAMP-dependent pathway. The translocation of PKCdelta and epsilon to the T-tubules was observed only after alpha(1A)-adrenoceptor stimulation, but not after alpha(1B)-adrenoceptor stimulation. Immunoprecipitation analysis revealed that alpha(1A)-adrenoceptor was associated with G(q/11), but alpha(1B)-adrenoceptor interacted with one of the pertussis toxin-sensitive G proteins, G(o). These findings demonstrated that the interactions of alpha(1)-adrenoceptor subtypes with different G proteins elicit the formation of separate signaling cascades, which produce the opposite effects on I(Ca). The coupling of alpha(1A)-adrenoceptor with G(q/11)-PLC-PKC-CaMKII pathway potentiates I(Ca). In contrast, alpha(1B)-adrenoceptor interacts with G(o), of which the betagamma-complex might directly inhibit the channel activity at T-tubules.
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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/(2-(2',6'-dimethoxy)phenoxyethylamin...,
http://linkedlifedata.com/resource/pubmed/chemical/A 61603,
http://linkedlifedata.com/resource/pubmed/chemical/Adra1a protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Adra1b protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels, L-Type,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/Dioxanes,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Pertussis Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Phenylephrine,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adrenergic, alpha-1,
http://linkedlifedata.com/resource/pubmed/chemical/Tetrahydronaphthalenes,
http://linkedlifedata.com/resource/pubmed/chemical/Type C Phospholipases
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jun
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| pubmed:issn |
1524-4571
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
6
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| pubmed:volume |
102
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1378-88
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:18467629-Animals,
pubmed-meshheading:18467629-Calcium Channels, L-Type,
pubmed-meshheading:18467629-Calcium-Calmodulin-Dependent Protein Kinase Type 2,
pubmed-meshheading:18467629-Cells, Cultured,
pubmed-meshheading:18467629-Dioxanes,
pubmed-meshheading:18467629-Enzyme Inhibitors,
pubmed-meshheading:18467629-GTP-Binding Proteins,
pubmed-meshheading:18467629-Heart Ventricles,
pubmed-meshheading:18467629-Imidazoles,
pubmed-meshheading:18467629-Myocytes, Cardiac,
pubmed-meshheading:18467629-Pertussis Toxin,
pubmed-meshheading:18467629-Phenylephrine,
pubmed-meshheading:18467629-Protein Kinase C,
pubmed-meshheading:18467629-Protein Transport,
pubmed-meshheading:18467629-Rats,
pubmed-meshheading:18467629-Receptors, Adrenergic, alpha-1,
pubmed-meshheading:18467629-Signal Transduction,
pubmed-meshheading:18467629-Tetrahydronaphthalenes,
pubmed-meshheading:18467629-Type C Phospholipases
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| pubmed:year |
2008
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| pubmed:articleTitle |
Interaction of alpha1-adrenoceptor subtypes with different G proteins induces opposite effects on cardiac L-type Ca2+ channel.
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| pubmed:affiliation |
Department of Cell Physiology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461 Japan. o-uchi@jikei.ac.jp
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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