Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2007-11-27
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.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
26
pubmed:volume
101
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1096-103
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Rescue of cGMP kinase I knockout mice by smooth muscle specific expression of either isozyme.
pubmed:affiliation
Institut für Pharmakologie und Toxikologie der Technischen Universität, Biedersteiner Str. 29, D-80802 München, Germany.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't