Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3 Pt 2
|
| pubmed:dateCreated |
1997-10-23
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| pubmed:abstractText |
Recent studies have shown that beta 2-adrenergic receptor (beta 2-AR)-stimulated increases in the intracellular Ca2+ (Cai) transient and contraction in cardiac myocytes are dissociated from the increase in adenosine 3',5'-cyclic monophosphate (cAMP) level and are not accompanied by an increase in phospholamban phosphorylation, an acceleration in relaxation, or a reduction in myofilament Ca2+ response. Thus we hypothesized that the beta 2-AR modulation of cardiac excitation-contraction (EC) coupling may be mediated by either a cAMP-independent mechanism or a compartmentalized cAMP pathway. To directly distinguish between these two possibilities, the responses of the L-type Ca2+ current (ICa), Cai transient, and contraction to beta 2-AR as well as to beta 1-AR stimulation were examined in rat ventricular myocytes in the presence or absence of specific inhibitory cAMP analogs, Rp diastereomers of adenosine 3',5'-cyclic monophosphothioate (Rp-cAMPS) and 8-(4-chlorophenylthio)-cAMP (Rp-CPT-cAMPS). As expected, the positive inotropic effect induced by an adenylyl cyclase activator, forskolin (2 x 10(-7) M), or a beta 1-AR agonist, norepinephrine (5 x 10(-8) M) plus prazosin (10(-6) M), was completely blocked by Rp-CPT-cAMPS. More importantly, the responses of ICa, Cai transient, and contraction to beta 2-AR stimulation by zinterol (10(-5) M) or isoproterenol plus a selective beta 1-AR antagonist, CGP-20712A, were also entirely abolished by Rp-cAMPS (in the patch-pipette solution) or Rp-CPT-cAMPS (in the bath solution). In pertussis toxin-treated cells, although the response of cAMP was not altered, the beta 2-AR-stimulated increase in contraction amplitude was markedly enhanced and accompanied by a hastened relaxation, resulting in a tight association between cAMP and contraction. These results indicate that beta 2-AR modulation of cardiac excitation-contraction coupling requires cAMP. The dissociation of beta 2-AR-stimulated cAMP production and regulation of myofilament and sarcoplasmic reticulum functions is attributable to a functional compartmentation of the cAMP-dependent signaling due to an activation of beta 2-AR-coupled Gi and/or G(o).
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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/Adrenergic beta-Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic beta-Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/CGP 20712A,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels, L-Type,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Ethanolamines,
http://linkedlifedata.com/resource/pubmed/chemical/Forskolin,
http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Isoproterenol,
http://linkedlifedata.com/resource/pubmed/chemical/Norepinephrine,
http://linkedlifedata.com/resource/pubmed/chemical/Prazosin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adrenergic, beta-2,
http://linkedlifedata.com/resource/pubmed/chemical/Thionucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/adenosine-3',5'-cyclic...,
http://linkedlifedata.com/resource/pubmed/chemical/zinterol
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
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| pubmed:issn |
0002-9513
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
273
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
H1611-8
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:9321856-Adrenergic beta-Agonists,
pubmed-meshheading:9321856-Adrenergic beta-Antagonists,
pubmed-meshheading:9321856-Animals,
pubmed-meshheading:9321856-Calcium,
pubmed-meshheading:9321856-Calcium Channels,
pubmed-meshheading:9321856-Calcium Channels, L-Type,
pubmed-meshheading:9321856-Cyclic AMP,
pubmed-meshheading:9321856-Ethanolamines,
pubmed-meshheading:9321856-Forskolin,
pubmed-meshheading:9321856-Heart,
pubmed-meshheading:9321856-Heart Ventricles,
pubmed-meshheading:9321856-Imidazoles,
pubmed-meshheading:9321856-Isoproterenol,
pubmed-meshheading:9321856-Myocardial Contraction,
pubmed-meshheading:9321856-Myocardium,
pubmed-meshheading:9321856-Norepinephrine,
pubmed-meshheading:9321856-Prazosin,
pubmed-meshheading:9321856-Rats,
pubmed-meshheading:9321856-Receptors, Adrenergic, beta-2,
pubmed-meshheading:9321856-Signal Transduction,
pubmed-meshheading:9321856-Thionucleotides
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| pubmed:year |
1997
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| pubmed:articleTitle |
Localized cAMP-dependent signaling mediates beta 2-adrenergic modulation of cardiac excitation-contraction coupling.
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| pubmed:affiliation |
Laboratory of Cardiovascular Science, National Institute on Aging, Baltimore, Maryland 21224, USA.
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| pubmed:publicationType |
Journal Article,
In Vitro
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