272 RHO-KINASE PATHWAY DIMINISHES THE RELAXATION EFFECT OF CYCLIC ADENOSINE MONOPHOSPHATE ON CARBACHOL-INDUCED CALCIUM SENSITIZATION IN CONTRACTION OF HUMAN DETRUSOR SMOOTH MUSCLE

Abstract

You have accessJournal of UrologyBladder and Urethra: Anatomy, Physiology and Pharmacology I1 Apr 2012272 RHO-KINASE PATHWAY DIMINISHES THE RELAXATION EFFECT OF CYCLIC ADENOSINE MONOPHOSPHATE ON CARBACHOL-INDUCED CALCIUM SENSITIZATION IN CONTRACTION OF HUMAN DETRUSOR SMOOTH MUSCLE Nouval Shahab, Shunichi Kajioka, Maya Hayashi, Takakazu Yunoki, and Seiji Naito Nouval ShahabNouval Shahab Fukuoka, Japan More articles by this author , Shunichi KajiokaShunichi Kajioka Fukuoka, Japan More articles by this author , Maya HayashiMaya Hayashi Fukuoka, Japan More articles by this author , Takakazu YunokiTakakazu Yunoki Fukuoka, Japan More articles by this author , and Seiji NaitoSeiji Naito Fukuoka, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.329AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The functional role of the cyclic adenosine monophosphate (cAMP) or the cyclic guanosine monophosphate (cGMP) pathways in the regulation of the detrusor smooth muscle (DSM) contraction through Ca2+ independent mechanism was assessed in α-toxin permeabilized human DSM. METHODS The DSM specimens were obtained from human urinary bladder who underwent radical cystectomy due to bladder cancer. The small DSM strips (3 - 4 mm in length and 300 - 400 μm in diameter) were prepared. After 60 minute permeabilization with α -toxin, the strips were horizontally mounted to transducer for isometric force recording. The experiment was carried out after pre-application with 1 μM A-23187 (Ca2+ ionophore) for 30 minutes and with 1 μM cyclopiazonic acid (Ca2+-ATPase inhibitor: CPA) whole through protocols. RESULTS While the adequate tension by 1 μM [Ca2+]i (the amplitude of the tension was normalized as 100 %) was observed , both cAMP and cGMP induced relaxation by 68.1 ± 4.7 % and 42.9 ± 6.5 %, respectively (P < 0.001; n = 8; Fig. A.1-3). Also, the contraction induced by cumulative addition of Ca2+ was significantly attenuated in the presence of 100 μM cAMP at all [Ca2+]i concentration but was slightly in the presence of 100 μM cGMP. The presence of 100 μM cAMP shifted the tension curve to the right increasing the EC50 significantly from 3.3 ± 0.1 μM to 9.5 ± 0.1 μM (P < 0.001; n = 6; Fig.B.1-4). Interestingly, the relaxation effect of 100 μM cAMP on contraction induced by 1 μM Ca2+ was diminished in muscarinic receptor activation by 10 μM CCh and 100 μM GTP. This inhibition was partially recovered in the presence of 1 μM AF-DX-116 and was remarkably potentiated in the presence of 1 μM Y-27632 (Fig. C.1-4). No effect of 100 μM cAMP on contraction induced by1 μM Ca2+ and 1 μM Calyculin A (Fig. D1 & 2). CONCLUSIONS This study demonstrated the predominant role of cAMP pathway in relaxation of human DSM contraction through Ca2+-desensitization by activation of myosine light chain phosphatase. The results of this study confirm the link of M2 receptor subtype with cAMP pathway and suggest the novel interaction between ROK and cAMP pathways. These findings are useful in the treatment strategy for patients with bladder dysfunction. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e110 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nouval Shahab Fukuoka, Japan More articles by this author Shunichi Kajioka Fukuoka, Japan More articles by this author Maya Hayashi Fukuoka, Japan More articles by this author Takakazu Yunoki Fukuoka, Japan More articles by this author Seiji Naito Fukuoka, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...