Effects of Rho-kinase inhibition on myosin light chain phosphorylation and obstruction-induced detrusor overactivity
Autor: | Maureen Basha, Sunish Mohanan, Joseph A. Hypolite, Samuel Chacko, Nicholas J. Laping, James O. Marx, Shaohua Chang, Stephen A. Zderic, Alan J. Wein |
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Rok vydání: | 2013 |
Předmět: |
Detrusor muscle
medicine.medical_specialty Myosin light-chain kinase biology business.industry Urology macromolecular substances medicine.disease biology.organism_classification Basal (phylogenetics) medicine.anatomical_structure New Zealand white rabbit Endocrinology Overactive bladder Rho kinase inhibitor Internal medicine medicine Phosphorylation business Rho-associated protein kinase |
Zdroj: | International Journal of Urology. 21:319-324 |
ISSN: | 0919-8172 |
Popis: | Objectives To study the relationship between myosin light chain phosphorylation of the detrusor muscle and spontaneous smooth muscle contractions in a rabbit model of partial outlet obstruction. Methods New Zealand white rabbit urinary bladders were partially obstructed for 2 weeks. Rabbits were euthanized, detrusor muscle strips were hung on a force transducer and spontaneous activity was measured at varying concentrations (0–0.03 μM/L) of the Rho-kinase inhibitors GSK 576371 or 0.01 μM/L Y27632. Basal myosin light chain phosphorylation was measured by 2-D gel electrophoresis in control and GSK 576371-treated strips. Results Both drugs suppressed the force of spontaneous contractions, whereas GSK 576371 had a more profound effect on the frequency of the contractions. The IC50 values for the inhibition of frequency and force of spontaneous contractions were 0.17 μM/L and 0.023 μM/L for GSK 576371, respectively. The compound significantly decreased the basal myosin light chain phosphorylation from 28.0 ± 3.9% to 13.5 ± 1.9% (P |
Databáze: | OpenAIRE |
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