Weber, Silke and Bernhard, Dominik and Lukowski, Robert and Weinmeister, Pascal and Woerner, Rene and Wegener, Joerg W. and Valtcheva, Nadejda and Feil, Susanne and Schlossmann, Jens and Hofmann, Franz and Feil, Robert (2007) Rescue of cGMP kinase I knockout mice by smooth muscle-specific expression of either isozyme. CIRCULATION RESEARCH, 101 (11). pp. 1096-1103. ISSN 0009-7330,
Full text not available from this repository. (Request a copy)Abstract
Smooth muscle expresses the I alpha and the I beta isoforms of cGMP- dependent protein kinase I (cGKI). Inactivation of the murine cGKI gene prkg1 leads to multiple phenotypes and premature death at approximate to 6 weeks. We reconstituted mice with the cGKI alpha or -I beta isozyme to test which isozyme was needed to support basic smooth muscle functions. Mice were generated by gene targeting. The cGKI alpha or the - I beta coding sequences were placed under the control of the SM22 alpha promoter to express either isoform selectively in smooth muscle cells ( SM-I alpha or SM-I beta transgene). To generate smooth muscle-specific cGKI alpha or cGKI beta rescue mice, the SM-I alpha or SM-I beta transgenes were crossed on a cGKI(-/-) genetic background. The levels of cGKI alpha or -I beta expression were comparable to endogenous cGKI expression in wild-type aortic and intestinal smooth muscles. In cGKI alpha or -I beta rescue mice, expression of the isozymes was not detectable in non-smooth muscle tissues and cells. Median survival time of the I alpha and I beta 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 cGKI alpha and cGKI beta 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DEPENDENT PROTEIN-KINASE; NITRIC-OXIDE; BLOOD-PRESSURE; CYCLIC-GMP; DEFICIENT MICE; IRAG; RELAXATION; RECEPTOR; BETA; PHOSPHATASE; cGMP kinase isozymes; PKG; nitric oxide; smooth muscle; blood pressure |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmacology and Toxicology (Prof. Schlossmann, formerly Prof. Seifert) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 25 Nov 2020 13:51 |
| Last Modified: | 25 Nov 2020 13:51 |
| URI: | https://pred.uni-regensburg.de/id/eprint/31900 |
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