Functional Coupling of Overexpressed β1-Adrenoceptors in the Myocardium of Transgenic Mice
| Autor: | Heiko Kilter, Markus Flesch, Michael Böhm, Petra Schnabel, Oliver Zolk, P. Mansier, Bernard Swynghedauw |
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| Rok vydání: | 1998 |
| Předmět: |
Genetically modified mouse
medicine.medical_specialty Gs alpha subunit G protein Transgene Biophysics Mice Transgenic Biology Biochemistry Adenylyl cyclase Mice chemistry.chemical_compound Chlorides GTP-Binding Proteins Internal medicine medicine Animals Humans Heart Atria Virulence Factors Bordetella Receptor Molecular Biology Crosses Genetic Adenosine Diphosphate Ribose Guanylyl Imidodiphosphate Forskolin Myocardium Colforsin Isoproterenol Heart Cell Biology Myocardial Contraction Molecular biology Mice Inbred C57BL Kinetics Endocrinology Manganese Compounds Pertussis Toxin chemistry Mice Inbred DBA Adenylate Cyclase Toxin Receptors Adrenergic beta-1 Signal transduction Adenylyl Cyclases Signal Transduction |
| Zdroj: | Biochemical and Biophysical Research Communications. 248:801-805 |
| ISSN: | 0006-291X |
| DOI: | 10.1006/bbrc.1998.9030 |
| Popis: | To assess functional and cellular effects of myocardial beta 1-adrenoceptor overexpression, alterations of the beta-adrenergic signal transduction pathway and contractile function in transgenic mice with atrial overexpression of the human beta 1-adrenoceptor were investigated. Radioligand binding experiments confirmed a 5- to 6-fold increase in beta-adrenoceptor density and a 2.7-fold increase in high-affinity binding sites in atria of transgenic mice. Dose-response curves for isoprenaline-induced force of contraction showed unchanged maximum effects but significantly increased pD2 values. Basal, MnCl2- and isoprenaline-stimulated adenylyl cyclase activities did not significantly differ, whereas the Gpp(NH)p and forskolin effect tends to be reduced in transgenic mice. The level of Gi alpha (pertussis toxin-catalyzed ADP-ribosylation) was unchanged, whereas the bioactivity of Gs alpha (reconstitution experiments into S49 cyc- cell membranes) was reduced by about 19% in the transgenic group. These results suggest that overexpressed beta 1-adrenoceptors act as functional spare receptors. In addition, increased beta 1-adrenoceptor density is associated with a decrease in Gs alpha-activity. |
| Databáze: | OpenAIRE |
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