183 ROLE OF MYOSIN LIGHT CHAIN PHOSPHORYLATION IN PARTIAL BLADDER OUTLET OBSTRUCTION: COMPENSATED VERSUS DECOMPENSATED

Abstract

You have accessJournal of UrologyBladder and Urethra: Anatomy, Physiology and Pharmacology I1 Apr 2010183 ROLE OF MYOSIN LIGHT CHAIN PHOSPHORYLATION IN PARTIAL BLADDER OUTLET OBSTRUCTION: COMPENSATED VERSUS DECOMPENSATED Joseph Hypolite, Shaohua Chang, Stephen Zderic, Alan Wein, Stephan Butler, and Samuel Chacko Joseph HypoliteJoseph Hypolite Lansdowne, PA More articles by this author , Shaohua ChangShaohua Chang Glenolden, PA More articles by this author , Stephen ZdericStephen Zderic Philadelphia, PA More articles by this author , Alan WeinAlan Wein Philadelphia, PA More articles by this author , Stephan ButlerStephan Butler Philadelphia, PA More articles by this author , and Samuel ChackoSamuel Chacko Glenolden, PA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.239AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Benign prostatic hyperplasia (BPH) in men can lead to bladder outlet obstruction(BOO). We have reported previously that BOO in the rabbit model can be categorized into compensated and decompensated based on bladder function studies obtained from metabolic cage data and in vitro biochemical and physiological studies. The compensated group maintains their function close to normal whereas the decompensated group demonstrates higher frequency of urination and low void volume. The bladder dysfunction is also associated with changes in contractile and regulatory proteins which control myosin phosphorylation, and can affect force generation of the bladder smooth muscle. In the present study, we ask what role myosin light chain (MLC20) phosphorylation plays in BOO-induced compensation and decompensation at the resting level, and upon activation with carbachol (50μM) and KCl (125mM). METHODS Adult male New Zealand white rabbits were partially obstructed by surgical ligation of the urethra, and sham-operated rabbits served as controls. Metabolic cage data analysis was used to segregate bladders into compensated and decompensated groups based on the frequency of urination and void volume over a 24 hour period. In vitro muscle strip studies and two-dimensional gel electrophoresis were used to study contractile function and MLC20 phosphorylation, respectively, in sham-operated and two week obstructed rabbit bladders. RESULTS Decompensated bladders showed a significant reduction in maximum force, and the rate of force generation in response to both KCl (47%) and carbachol (41%) compared to compensated and sham bladders. Both the resting level of MLC20 phosphorylation (13%) and the level at maximum force generation (23%) were significantly less in decompensated bladders compared to sham and compensated bladders (23% at resting level and 36% at maximum force). There was no significant difference in the basal, or maximal phosphorylation level in response to KCl and carbachol between sham and compensated bladders. The mean weights of the bladders were, 2.2, 4.8 and 10.4 grams for sham, compensated and decompensated respectively. CONCLUSIONS Since MLC20 phosphorylation is the primary mechanism involved in smooth muscle contraction, the data suggests that the reduced levels of MLC20 phosphorylation both at rest and upon activation, in the decompensated bladders may be a major contributing factor to the contractile dysfunction seen in these bladders. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e73 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joseph Hypolite Lansdowne, PA More articles by this author Shaohua Chang Glenolden, PA More articles by this author Stephen Zderic Philadelphia, PA More articles by this author Alan Wein Philadelphia, PA More articles by this author Stephan Butler Philadelphia, PA More articles by this author Samuel Chacko Glenolden, PA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...