Document Detail

Correlation between pharmacologically-induced changes in cystometric parameters and spinal c-Fos expression in rats.
MedLine Citation:
PMID:  20335078     Owner:  NLM     Status:  MEDLINE    
The inhibition of bladder sensory transmission is critical for the pharmacotherapy of urine storage symptoms. The purpose of this study is to examine the correlation between pharmacologically-induced changes in cystometric parameters and spinal c-Fos expression in anesthetized rats with bladder hyperactivity induced by the intravesical infusion of acetic acid. Animals were intravenously infused with either oxybutynin (OXY), a muscarinic receptor antagonist, tamsulosin (TAM), an alpha1-adrenoceptor antagonist, CL316243 (CL), a beta3-adrenoceptor agonist, or saline. Morphine (MOR) treatment served as a positive control to inhibit bladder afferent activity. Intermicturition intervals, micturition pressure and pressure threshold were measured after intravesical acetic acid infusion. Animals were then perfused and spinal cords were removed. Sections from the L6 spinal cord were immunostained with an anti-c-Fos antibody, and c-Fos positive cells in the dorsal region were counted. CL and MOR significantly increased intermicturition intervals, whereas OXY and TAM had no significant effect on intermicturition intervals. While TAM and MOR did not affect the micturition pressure, OXY and CL caused a significant decrease. Pressure threshold was significantly decreased by CL and increased by MOR. All drugs significantly decreased the number of c-Fos positive cells with the following order of efficacy: MOR>CL>OXT>TAM. The number of c-Fos positive cells in each animal from all treatment groups was negatively correlated with its average intermicturition interval and pressure threshold, but not with its micturition pressure. Bladder afferent activity is suppressed by several clinically proven mechanisms as measured by c-Fos expression, despite the varied effects on cystometric parameters of each pharmacological treatment.
Hiroshi Nagabukuro; Amanda Degenhardt; Katherine L Villa; Shruti L Mistry; Loise Gichuru; Nina Jochnowitz; Catherine Abbadie
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Publication Detail:
Type:  Comparative Study; Journal Article     Date:  2010-03-24
Journal Detail:
Title:  Autonomic neuroscience : basic & clinical     Volume:  156     ISSN:  1872-7484     ISO Abbreviation:  Auton Neurosci     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-02     Completed Date:  2011-04-26     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  100909359     Medline TA:  Auton Neurosci     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  19-26     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier B.V. All rights reserved.
Department of Musculo-Skeletal, Merck Research Laboratories, Boston, MA, USA.
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MeSH Terms
Dioxoles / pharmacology
Gene Expression Regulation / drug effects
Mandelic Acids / pharmacology
Proto-Oncogene Proteins c-fos / biosynthesis*
Rats, Sprague-Dawley
Spinal Cord / drug effects*,  metabolism*
Sulfonamides / pharmacology
Urinary Bladder / drug effects*,  physiology*
Urination / drug effects,  genetics
Reg. No./Substance:
0/Dioxoles; 0/Mandelic Acids; 0/Proto-Oncogene Proteins c-fos; 0/Sulfonamides; 138908-40-4/disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; 5633-20-5/oxybutynin; G3P28OML5I/tamsulosin

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