Source:http://linkedlifedata.com/resource/pubmed/id/17901360
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
11
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pubmed:dateCreated |
2007-11-27
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pubmed:abstractText |
Smooth muscle expresses the Ialpha and the Ibeta isoforms of cGMP-dependent protein kinase I (cGKI). Inactivation of the murine cGKI gene prkg1 leads to multiple phenotypes and premature death at approximately 6 weeks. We reconstituted mice with the cGKIalpha or -Ibeta isozyme to test which isozyme was needed to support basic smooth muscle functions. Mice were generated by gene targeting. The cGKIalpha or the -Ibeta coding sequences were placed under the control of the SM22alpha promoter to express either isoform selectively in smooth muscle cells (SM-Ialpha or SM-Ibeta transgene). To generate smooth muscle-specific cGKIalpha or cGKIbeta rescue mice, the SM-Ialpha or SM-Ibeta transgenes were crossed on a cGKI-/- genetic background. The levels of cGKIalpha or -Ibeta expression were comparable to endogenous cGKI expression in wild-type aortic and intestinal smooth muscles. In cGKIalpha or -Ibeta rescue mice, expression of the isozymes was not detectable in non-smooth muscle tissues and cells. Median survival time of the Ialpha and Ibeta rescue mice was 52 weeks. Both isozymes mediated the 8-bromo-cGMP-induced relaxation of precontracted jejunum and aorta muscle strips. Activation of both isozymes reduced hormone- or K+-induced [Ca2+]i levels. The cGKIalpha and cGKIbeta rescue mice did not show a significant difference in intestinal passage time of BaSO4 in comparison with wild-type animals. Telemetric blood pressure measurements in conscious freely moving animals did not show differences between rescues and control mice in basal blood pressure and its regulation by DETA-NO, sodium nitroprusside, carbachol, or Y-27632. These results show that cGKI in smooth muscle is essential and that either cGKI isozyme alone can rescue basic vascular and intestinal smooth muscle functions.
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pubmed:commentsCorrections | |
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/Cyclic GMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic GMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/cGMP-dependent protein kinase Ialpha
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1524-4571
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pubmed:author |
pubmed-author:BernhardDominikD,
pubmed-author:FeilRobertR,
pubmed-author:FeilSusanneS,
pubmed-author:HofmannFranzF,
pubmed-author:LukowskiRobertR,
pubmed-author:SchlossmannJensJ,
pubmed-author:ValtchevaNadejdaN,
pubmed-author:WörnerRenéR,
pubmed-author:WeberSilkeS,
pubmed-author:WegenerJörg WJW,
pubmed-author:WeinmeisterPascalP
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pubmed:issnType |
Electronic
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pubmed:day |
26
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pubmed:volume |
101
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1096-103
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17901360-Animals,
pubmed-meshheading:17901360-Aorta,
pubmed-meshheading:17901360-Blood Pressure,
pubmed-meshheading:17901360-Calcium,
pubmed-meshheading:17901360-Cyclic GMP,
pubmed-meshheading:17901360-Cyclic GMP-Dependent Protein Kinases,
pubmed-meshheading:17901360-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:17901360-Isoenzymes,
pubmed-meshheading:17901360-Jejunum,
pubmed-meshheading:17901360-Mice,
pubmed-meshheading:17901360-Mice, Knockout,
pubmed-meshheading:17901360-Muscle, Smooth,
pubmed-meshheading:17901360-Muscle Relaxation,
pubmed-meshheading:17901360-Survival Rate
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pubmed:year |
2007
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pubmed:articleTitle |
Rescue of cGMP kinase I knockout mice by smooth muscle specific expression of either isozyme.
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pubmed:affiliation |
Institut für Pharmakologie und Toxikologie der Technischen Universität, Biedersteiner Str. 29, D-80802 München, Germany.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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