Prostaglandin E2 excitatory effects on rat urinary bladder: a comparison between the β-adrenoceptor modulation of non-voiding activity in vivo and micro-contractile activity in vitro

2015 ◽  
Vol 388 (7) ◽  
pp. 727-735 ◽  
Author(s):  
C. Granato ◽  
C. Korstanje ◽  
V. Guilloteau ◽  
C. Rouget ◽  
S. Palea ◽  
...  
Keyword(s):  
Urinary Bladder ◽  
Prostaglandin E2 ◽  
Contractile Activity ◽  
Rat Urinary Bladder

scholarly journals Rat Urinary Bladder Carcinogenesis by Dual-Acting PPARα+γAgonists

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-14 ◽  
Author(s):  
Martin B. Oleksiewicz ◽  
Jennifer Southgate ◽  
Lars Iversen ◽  
Frederikke L. Egerod
Keyword(s):  
Urinary Bladder ◽  
Mode Of Action ◽  
Carcinogenic Effect ◽  
Attrition Rates ◽  
Rat Urinary Bladder ◽  
Mediated Effects ◽  
Kidney Pelvis ◽  
Rats And Mice

Despite clinical promise, dual-acting activators of PPARαandγ(here termed PPARα+γagonists) have experienced high attrition rates in preclinical and early clinical development, due to toxicity. In some cases, discontinuation was due to carcinogenic effect in the rat urothelium, the epithelial layer lining the urinary bladder, ureters, and kidney pelvis. Chronic pharmacological activation of PPARαis invariably associated with cancer in rats and mice. Chronic pharmacological activation of PPARγcan in some cases also cause cancer in rats and mice. Urothelial cells coexpress PPARαas well as PPARγ, making it plausible that the urothelial carcinogenicity of PPARα+γagonists may be caused by receptor-mediated effects (exaggerated pharmacology). Based on previously published mode of action data for the PPARα+γagonist ragaglitazar, and the available literature about the role of PPARαandγin rodent carcinogenesis, we propose a mode of action hypothesis for the carcinogenic effect of PPARα+γagonists in the rat urothelium, which combines receptor-mediated and off-target cytotoxic effects. The proposed mode of action hypothesis is being explored in our laboratories, towards understanding the human relevance of the rat cancer findings, and developing rapid in vitro or short-term in vivo screening approaches to faciliate development of new dual-acting PPAR agonist compounds.

Kinin receptors in experimental inflammation

1980 ◽  
Vol 58 (5) ◽  
pp. 536-542 ◽  
Author(s):  
F. Marceau ◽  
J. Barabé ◽  
S. St-Pierre ◽  
D. Regoli
Keyword(s):  
Urinary Bladder ◽  
De Novo ◽  
Rabbit Aorta ◽  
Initial Response ◽  
Rat Urinary Bladder ◽  
Chemical Mediation ◽  
Intravesical Injection ◽  
Triton X

The contractile response of the rat isolated urinary bladder to kinins is mediated by receptors of the B1 and of the B2 types, as this preparation responds to des-Arg9-bradykinin (des-Arg9-BK), a fairly selective stimulant of receptor B1 and to [Tyr(Me)8]-BK, a potent agonist on receptor B2. Des-Arg10-[Leu9]-kallidin, a specific and competitive antagonist of the action of kinins on receptor B1, has been found to block the effect of des-Arg9-BK in concentrations similar to those required in the rabbit aorta; therefore, the B1 receptor of the rat urinary bladder is analogous to that of the rabbit vascular tissue.The response of the rat urinary bladder to des-Arg9-BK increases progressively from near null level during the incubation in vitro and can be abolished by cycloheximide; this suggests that receptor B1 of the rat urinary bladder is formed de novo.The inflammation of the bladder induced by intravesical injection of the detergent Triton X-100 enhances the initial response to des-Arg9-BK without modifying the response to other agents. The B1 receptor is formed in vivo in the rat urinary bladder submitted to the Triton X-100 treatment but not in the control untreated organ. The local de novo synthesis of B1 receptors for kinins that follows a noxious stimulus is proposed as a possible mechanism implicated in the chemical mediation of the inflammatory process.

Expression of cyclooxygenase-1 and -2 in urinary bladder carcinomas in vivo and in vitro and prostaglandin E2 synthesis in cultured bladder cancer cells

Pathology ◽  
2001 ◽  
Vol 33 (4) ◽  
pp. 469-474 ◽  
Author(s):  
Peter J. Boström ◽  
Vesa Aaltonen ◽  
Karl-Ove Söderström ◽  
Pekka Uotila ◽  
Matti Laato
Keyword(s):  
Bladder Cancer ◽  
Urinary Bladder ◽  
Prostaglandin E2 ◽  
Cancer Cells ◽  
Cyclooxygenase 1 ◽  
Bladder Cancer Cells ◽  
Bladder Carcinomas

scholarly journals Genetic deletion of trkB.T1 increases neuromuscular function

2012 ◽  
Vol 302 (1) ◽  
pp. C141-C153 ◽  
Author(s):  
Susan G. Dorsey ◽  
Richard M. Lovering ◽  
Cynthia L. Renn ◽  
Carmen C. Leitch ◽  
Xinyue Liu ◽  
...  
Keyword(s):  
Calcium Release ◽  
Contractile Activity ◽  
Muscle Tension ◽  
Neuromuscular Synapse ◽  
Neuromuscular Function ◽  
In Vitro Assays ◽  
Tyrosine Kinase Receptor ◽  
Akt Activation

Neurotrophin-dependent activation of the tyrosine kinase receptor trkB.FL modulates neuromuscular synapse maintenance and function; however, it is unclear what role the alternative splice variant, truncated trkB ( trkB.T1), may have in the peripheral neuromuscular axis. We examined this question in trkB.T1 null mice and demonstrate that in vivo neuromuscular performance and nerve-evoked muscle tension are significantly increased. In vitro assays indicated that the gain-in-function in trkB.T1 −/− animals resulted specifically from an increased muscle contractility, and increased electrically evoked calcium release. In the trkB.T1 null muscle, we identified an increase in Akt activation in resting muscle as well as a significant increase in trkB.FL and Akt activation in response to contractile activity. On the basis of these findings, we conclude that the trkB signaling pathway might represent a novel target for intervention across diseases characterized by deficits in neuromuscular function.

In vitro and in vivo relaxation of urinary bladder smooth muscle by the selective myosin II inhibitor, blebbistatin

2011 ◽  
Vol 107 (2) ◽  
pp. 310-317 ◽  
Author(s):  
Xinhua Zhang ◽  
Dwaraka Srinivasa R. Kuppam ◽  
Arnold Melman ◽  
Michael E. DiSanto
Keyword(s):  
Smooth Muscle ◽  
Urinary Bladder ◽  
Myosin Ii ◽  
Bladder Smooth Muscle ◽  
Urinary Bladder Smooth Muscle

Evaluation of the bioactivity about anti-sca-1/basic fibroblast growth factor-urinary bladder matrix scaffold for pelvic reconstruction

2018 ◽  
Vol 33 (6) ◽  
pp. 808-818 ◽  
Author(s):  
Jiankui Li ◽  
Xi Chen ◽  
Kaijian Ling ◽  
Zhiqing Liang ◽  
Huicheng Xu
Keyword(s):  
Growth Factor ◽  
Urinary Bladder ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Pelvic Organ ◽  
Fibroblast Growth ◽  
Pelvic Reconstruction ◽  
Urinary Bladder Matrix

Introduction and hypothesis: Pelvic support structure injury is the major cause of pelvic organ prolapse. At present, polypropylene-based filler material has been suggested as a common method to treat pelvic organ prolapse. However, it cannot functionally rehabilitate the pelvic support structure. In addition to its poor long-term efficiency, the urinary bladder matrix was the most suitable biological scaffold material for pelvic floor repair. Here, we hypothesize that anti-sca-1 monoclonal antibody and basic fibroblast growth factor were cross-linked to urinary bladder matrix to construct a two-factor bioscaffold for pelvic reconstruction. Methods Through a bispecific cross-linking reagent, sulfosuccinimidyl 4-[N-maleimidomethyl] cyclohexane-1-carboxylate (sulfo-smcc) immobilized anti-sca-1 and basic fibroblast growth factor to urinary bladder matrix. Then scanning electron microscope and plate reader were used to detect whether the anti-sca-1/basic fibroblast growth factor-urinary bladder matrix scaffold was built successfully. After that, the capacity of enriching sca-1 positive cells was measured both in vitro and in vivo. In addition, we evaluated the differentiation capacity and biocompatibility of the scaffold. Finally, western blotting was used to detect the level of fibulin-5 protein. Results The scanning electron microscope and plate reader revealed that the double-factor biological scaffold was built successfully. The scaffold could significantly enrich a large number of sca-1 positive cells both in vitro and in vivo, and obviously accelerate cells and differentiate functional tissue with good biocompatibility. Moreover, the western blotting showed that the scaffold could improve the expression of fibulin-5 protein. Conclusion The anti-sca-1/basic fibroblast growth factor-urinary bladder matrix scaffold revealed good biological properties and might serve as an ideal scaffold for pelvic reconstruction.

Sign in / Sign up

Export Citation Format

Share Document