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Inducible nitric oxide synthase increases secretion from inflamed salivary glands

Objective. Salivary gland secretion is dependent on cholinergic stimulation via autonomic nerves and calcium signalling in acinar cells. Secretory dysfunction associated with SS may be partly caused by the damaging effects of increased glandular concentrations of nitric oxide (NO) derived from up-re...

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Autores principales: Correia, Patricia N., Carpenter, Guy H., Paterson, Katherine L., Proctor, Gordon B.
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2789584/
https://www.ncbi.nlm.nih.gov/pubmed/19933597
http://dx.doi.org/10.1093/rheumatology/kep313
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author Correia, Patricia N.
Carpenter, Guy H.
Paterson, Katherine L.
Proctor, Gordon B.
author_facet Correia, Patricia N.
Carpenter, Guy H.
Paterson, Katherine L.
Proctor, Gordon B.
author_sort Correia, Patricia N.
collection PubMed
description Objective. Salivary gland secretion is dependent on cholinergic stimulation via autonomic nerves and calcium signalling in acinar cells. Secretory dysfunction associated with SS may be partly caused by the damaging effects of increased glandular concentrations of nitric oxide (NO) derived from up-regulation of inducible NO synthase (iNOS) that accompanies glandular inflammation. The present study examines the effects of increased iNOS expression on salivary gland secretory function. Methods. The inflammogen lipopolysaccharide (LPS) was introduced intraductally into rat submandibular glands, and glandular responsiveness to cholinergic stimulation was determined. Results. LPS provoked a rapid, long-lasting inflammation, increasing gland weight (by almost 20%) and inflammatory cell infiltration at 3 and 24 h. Immunoblotting of glandular homogenates indicated that iNOS expression was increased ∼4-fold, and immunohistochemistry of frozen tissue sections showed increased iNOS expression in acinar cells. Salivary secretion from inflamed glands was significantly increased in response to low doses of methacholine and accompanied by increased acinar cell calcium signalling in vitro. Prior administration of the iNOS inhibitors, aminoguanidine or l-NIL [l-N6-(1-iminoethyl)-lysine dihydrochloride] abolished increased secretion and acinar cell calcium signalling. Conclusions. Up-regulation of glandular iNOS expression can increase cholinergically evoked salivary secretion and appears to offset any secretory hypofunction linked with glandular inflammation. It seems unlikely that increased glandular levels of NO are responsible for the secretory hypofunction that accompanies SS.
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spelling pubmed-27895842009-12-10 Inducible nitric oxide synthase increases secretion from inflamed salivary glands Correia, Patricia N. Carpenter, Guy H. Paterson, Katherine L. Proctor, Gordon B. Rheumatology (Oxford) Basic Science Objective. Salivary gland secretion is dependent on cholinergic stimulation via autonomic nerves and calcium signalling in acinar cells. Secretory dysfunction associated with SS may be partly caused by the damaging effects of increased glandular concentrations of nitric oxide (NO) derived from up-regulation of inducible NO synthase (iNOS) that accompanies glandular inflammation. The present study examines the effects of increased iNOS expression on salivary gland secretory function. Methods. The inflammogen lipopolysaccharide (LPS) was introduced intraductally into rat submandibular glands, and glandular responsiveness to cholinergic stimulation was determined. Results. LPS provoked a rapid, long-lasting inflammation, increasing gland weight (by almost 20%) and inflammatory cell infiltration at 3 and 24 h. Immunoblotting of glandular homogenates indicated that iNOS expression was increased ∼4-fold, and immunohistochemistry of frozen tissue sections showed increased iNOS expression in acinar cells. Salivary secretion from inflamed glands was significantly increased in response to low doses of methacholine and accompanied by increased acinar cell calcium signalling in vitro. Prior administration of the iNOS inhibitors, aminoguanidine or l-NIL [l-N6-(1-iminoethyl)-lysine dihydrochloride] abolished increased secretion and acinar cell calcium signalling. Conclusions. Up-regulation of glandular iNOS expression can increase cholinergically evoked salivary secretion and appears to offset any secretory hypofunction linked with glandular inflammation. It seems unlikely that increased glandular levels of NO are responsible for the secretory hypofunction that accompanies SS. Oxford University Press 2010-01 2009-11-20 /pmc/articles/PMC2789584/ /pubmed/19933597 http://dx.doi.org/10.1093/rheumatology/kep313 Text en © The Author(s) 2009. Published by Oxford University Press on behalf of The British Society for Rheumatology. http://creativecommons.org/licenses/by-nc/2.5/uk/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Basic Science
Correia, Patricia N.
Carpenter, Guy H.
Paterson, Katherine L.
Proctor, Gordon B.
Inducible nitric oxide synthase increases secretion from inflamed salivary glands
title Inducible nitric oxide synthase increases secretion from inflamed salivary glands
title_full Inducible nitric oxide synthase increases secretion from inflamed salivary glands
title_fullStr Inducible nitric oxide synthase increases secretion from inflamed salivary glands
title_full_unstemmed Inducible nitric oxide synthase increases secretion from inflamed salivary glands
title_short Inducible nitric oxide synthase increases secretion from inflamed salivary glands
title_sort inducible nitric oxide synthase increases secretion from inflamed salivary glands
topic Basic Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2789584/
https://www.ncbi.nlm.nih.gov/pubmed/19933597
http://dx.doi.org/10.1093/rheumatology/kep313
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