Document Detail

Refractoriness of urethral striated muscle contractility to nitric oxide-dependent cyclic GMP production.
MedLine Citation:
PMID:  20362065     Owner:  NLM     Status:  MEDLINE    
The purpose of this study was to investigate the role of cyclic GMP (cGMP) in the effects of nitric oxide (NO) on urethral striated muscle and its involvement in contractile function. The localization of cGMP, neuronal NO synthase (nNOS), vimentin, and neuronal markers was assessed by immunofluorescence in the sheep and rat urethra and the expression of nNOS was determined in Western blots. Nerve-mediated contractile responses to electrical field stimulation (EFS) were recorded in the sheep urethra. The scant nitrergic innervation of the striated muscle layer suggests that autonomic control of its activity is unlikely. The striated fiber itself may be the source of high levels NO produced by sarcolemmal and/or cytosolic mu or alpha variant of nNOS. This endogenous NO may provoke high basal production of soluble guanylate cyclase (GC) dependent cGMP, mainly in non-NO producing muscle fibers, which is not further enhanced by NO donors. cGMP co-localizes with neurofilament and PGP 9.5 at muscle endplates. Modulators of the cGMP pathway did not affect nerve-mediated contractile activity induced by EFS, suggesting that cGMP is not a significant mediator of neuromuscular transmission. In addition, NO donors did increase the accumulation of cGMP in dense networks of vimentin immunoreactive interstitial cells of Cajal (ICC), whose function is not yet known. These data suggest that there is a strong but non-regulated production of cGMP under resting conditions, which does not seem to affect contractile function. Modulation of cholinergic neurotransmission by NO through cGMP-independent mechanisms cannot be discarded.
Angeles Garcia-Pascual; Alicia Labadía; Marta Garcia-Flores; María Sancho; Domingo Triguero
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-31
Journal Detail:
Title:  Nitric oxide : biology and chemistry / official journal of the Nitric Oxide Society     Volume:  23     ISSN:  1089-8611     ISO Abbreviation:  Nitric Oxide     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-05-20     Completed Date:  2010-09-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9709307     Medline TA:  Nitric Oxide     Country:  United States    
Other Details:
Languages:  eng     Pagination:  26-33     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2010 Elsevier Inc. All rights reserved.
Department of Physiology, Veterinary School, Complutense University, Madrid, Spain.
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MeSH Terms
Blotting, Western
Cyclic GMP / biosynthesis*,  metabolism
Electric Stimulation
Microscopy, Fluorescence
Muscle Contraction / physiology*
Muscle, Striated / metabolism*
Neuromuscular Junction / metabolism
Nitric Oxide / metabolism
Nitric Oxide Synthase Type I / metabolism
Rats, Wistar
Urethra / cytology,  metabolism,  physiology*
Vimentin / metabolism
Reg. No./Substance:
0/Vimentin; 10102-43-9/Nitric Oxide; 7665-99-8/Cyclic GMP; EC Oxide Synthase Type I

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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