Functional characteristics of urinary tract smooth muscles in mice lacking cGMP protein kinase type I
| Autor: | Karl-Erik Andersson, Raj Kumar Pandita, Alexander Pfeifer, Marianne Ahmad, Reinhard Fässler, Katarina Persson, Attila Aszódi |
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| Rok vydání: | 2000 |
| Předmět: |
Male
medicine.medical_specialty Physiology Ratón Transgene Urinary system Urinary Bladder 8-Bromo Cyclic Adenosine Monophosphate Nitric Oxide Synthase Type I Cholinergic Agonists Biology Gene Expression Regulation Enzymologic Nitric oxide Mice chemistry.chemical_compound Urethra Physiology (medical) Internal medicine Cyclic GMP-Dependent Protein Kinases medicine Animals Protein kinase A Cyclic GMP Mice Knockout chemistry.chemical_classification Colforsin Muscle Smooth Immunohistochemistry Electric Stimulation Nitric oxide synthase Endocrinology Enzyme chemistry biology.protein Carbachol Female Nitric Oxide Synthase medicine.symptom Muscle Contraction Muscle contraction |
| Zdroj: | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 279:R1112-R1120 |
| ISSN: | 1522-1490 0363-6119 |
| Popis: | Nitric oxide (NO)-mediated smooth muscle relaxation is mediated by cGMP through activation of cGMP-dependent protein kinase I (cGKI). We studied the importance of cGKI for lower urinary tract function in mice lacking the gene for cGKI (cGKI−/−) and in litter-matched wild-type mice (cGKI+/+) in vitro and in vivo. cGKI deficiency did not result in any changes in bladder gross morphology or weight. Urethral strips from cGKI−/− mice showed an impaired relaxant response to nerve-derived NO. The cGMP analog 8-bromo-cGMP (8-BrcGMP) and the NO-donor SIN-1 relaxed the wild-type urethra (50–60%) but had only marginal effects in the cGKI-deficient urethra. Bladder strips from cGKI−/− mice responded normally to electrical field stimulation and to carbachol but not to 8-BrcGMP. In vivo, the cGKI-deficient mice showed bladder hyperactivity characterized by decreased intercontraction intervals and nonvoiding bladder contractions. Loss of cGKI abolishes NO-cGMP-dependent relaxations of urethral smooth muscle and results in hyperactive voiding. These data suggest that certain voiding disturbances may be associated with impaired NO-cGKI signaling. |
| Databáze: | OpenAIRE |
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