Age-dependent contribution of Rho kinase in carbachol-induced contraction of human detrusor smooth muscle in vitro

Kirschstein, Timo; Protzel, Chris; Porath, Katrin; Sellmann, Tina; Köhling, Rüdiger; Hakenberg, Oliver W
January 2014
Acta Pharmacologica Sinica;Jan2014, Vol. 35 Issue 1, p74
Academic Journal
Aim:Activation of muscarinic receptors on the detrusor smooth muscle is followed by contraction, which involves both myosin light chain kinase (MLCK) and Rho kinase (ROCK). The aim of this study was to determine the relative contributions of MLCK and ROCK to carbachol-induced contraction of human detrusor smooth muscle in vitro.Methods:Detrusor smooth muscle strips were prepared from the macroscopically unaffected bladder wall of patients underwent cystectomy. The strips were fixed in an organ bath, and carbachol or KCl-induced isometric contractions were measured by force transducers.Results:Addition of carbachol (0.4-4 μmol/L) into the bath induced concentration-dependent contractions of detrusor specimens, which was completely abolished by atropine (1 μmol/L). Pre-incubation of detrusor specimens with either the MLCK inhibitor ML-9 or the ROCK inhibitors HA1100 and Y-27632 (each at 10 μmol/L) significantly blocked carbachol-induced contractions as compared to the time-control experiments. Moreover, MLCK and ROCK inhibition were equally effective in reducing carbachol-induced contractions. The residual carbachol-induced contractions in the presence of both MLCK and ROCK inhibitors were significantly smaller than the contractions obtained when only one enzyme (either MLCK or ROCK) was inhibited, suggesting an additive effect of the two kinases. Interestingly, ROCK-mediated carbachol-induced contractions were positively correlated to the age of patients (r=o.52, P<0.05).Conclusion:Both MLCK and ROCK contribute to carbachol-induced contractions of human detrusor smooth muscle. ROCK inhibitors may be a new pharmacological approach to modulate human bladder hyperactivity.


Related Articles

  • Toviaz.  // Formulary;Dec2008, Vol. 43 Issue 12, p434 

    The article focuses on the drug Toviaz (Fesoterodine Fumarate). Muscairinillc receptor antagonist has been approved for the treatment of overactive bladder. Fesoterodine is a muscarinic receptor antagonist which produces its effects by governing the receptors that affect urinary bladder smooth...

  • Carbachol-Induced Volume Adaptation in Mouse Bladder and Length Adaptation via Rhythmic Contraction in Rabbit Detrusor. Speich, John; Wilson, Cameron; Almasri, Atheer; Southern, Jordan; Klausner, Adam; Ratz, Paul // Annals of Biomedical Engineering;Oct2012, Vol. 40 Issue 10, p2266 

    The length-tension ( L- T) relationships in rabbit detrusor smooth muscle (DSM) are similar to those in vascular and airway smooth muscles and exhibit short-term length adaptation characterized by L- T curves that shift along the length axis as a function of activation and strain history. In...

  • Inverse relationship of Rho kinase and myosin-light chain kinase expression in the aging human detrusor smooth muscle. Kirschstein, Timo; Sahre, Theresa; Kernig, Karoline; Protzel, Chris; Porath, Katrin; Köhling, Rüdiger; Hakenberg, Oliver W. // BMC Urology;10/15/2015, Vol. 15, p1 

    Background: Rho kinase (ROCK) and myosin-light chain kinase (MLCK) are key enzymes in smooth muscle contraction. Previous data have suggested that ROCK contribution to human detrusor contraction is increasing with age. Here, we have analyzed the transcriptional expression of Rho...

  • Rho-kinase expression in Hirschsprung's disease. Coyle, David; O'Donnell, Anne; Corcionivoschi, Nicolae; Gillick, John; Puri, Prem; O'Donnell, Anne Marie // Pediatric Surgery International;Nov2015, Vol. 31 Issue 11, p1077 

    Background: Rho-kinase (ROCK) is the primary effector protein in the RhoA pathway, which regulates Ca(2+)-independent smooth muscle contraction in the human bowel. This pathway has been reported to be hyper-activated in the aganglionic bowel of EDNRB-null (-/-) rats compared to the...

  • Rho-Kinase Inhibitors: Newer Therapeutic Target for Arteriosclerotic Diseases. Patel, V. M.; Gohil, P. V. // Journal of Pharmacy Research;Oct2010, Vol. 3 Issue 10, p2350 

    Cardiovascular diseases (comprise a group of diseases like, hypertension, various arteriosclerotic disease (ARDs), coronary and cerebral vasospasm etc.) are one of the leading causes of morbidity and mortality throughout the world. Wide variety of medications are used for the treatment of ARDs,...

  • The anti-fibrillatory effect of the acetylcholine analogue, Carbamylcholine, is dependent upon muscarinic and nicotinic receptor stimulation and the generation of NO. Kalla, M.; Coughlan, C.; Chotalia, M.; Hao, G.; Bub, G.; Paterson, D. J.; Herring, N. // Proceedings of the Physiological Society;2014, p110P 

    An abstract of the article "The anti-fibrillatory effect of the acetylcholine analogue, Carbamylcholine, is dependent upon muscarinic and nicotinic receptor stimulation and the generation of NO" by M. Kalla, C. Coughlan, M. Chotalia, G. Hao, G. Bub, D. J. Paterson, and N. Herring is presented.

  • Thermal influence of saliva secretion ex vivo in the mouse submandibular gland. Taro Mukaibo; Tetsuji Nakamoto; Yusuke Kondo; Manami Kidokoro; Atsushi Imamura; Chihiro Masaki; Ryuji Hosokawa // Open Journal of Stomatology;Mar2013, Vol. 3 Issue 1, p83 

    The physiological and pharmacological responses of an ex vivo mouse submandibular gland were used to study fluid secretion and cell signaling in response to muscarinic stimulation at increasing temperatures. Saliva production at 37°C was 5.5-fold that at 25°C with pilocarpine stimulation...

  • Circumferential stretching of saphenous vein smooth muscle enhances vasoconstrictor responses by Rho kinase-dependent pathways. McGregor, Emma; Gosling, Martin; Beattie, David K; Ribbons, Duncan M.P; Davies, Alun H; Powell, Janet T // Cardiovascular Research;Jan2002, Vol. 53 Issue 1, p219 

    Objective: Surgical preparation and/or pulsatile arterial perfusion of saphenous vein increases the sensitivity of vein rings to calcium mobilising agonists such as phenylephrine. We have investigated the mechanism(s) underlying this effect. Methods: We have used an ex vivo flow circuit, with...

  • Simvastatin Increases Fibulin-2 Expression in Human Coronary Artery Smooth Muscle Cells via RhoA/Rho-Kinase Signaling Pathway Inhibition. Serra, Noemí; Rosales, Roser; Masana, Lluís; Vallvé, Joan-Carles // PLoS ONE;7/24/2015, Vol. 10 Issue 7, p1 

    The composition and structure of the extracellular matrix (ECM) in the vascular wall and in the atherosclerotic plaque are important factors that determine plaque stability. Statins can stabilize atherosclerotic plaques by modulating ECM protein expression. Fibulins are important components of...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics