A role for nitric oxide-mediated glandular hypofunction in a non-apoptotic model for Sjogren's syndrome.

Caulfield, Vicky L, Balmer, Colette, Dawson, Luke J ORCID: 0000-0002-3807-932X and Smith, Peter M
(2009) A role for nitric oxide-mediated glandular hypofunction in a non-apoptotic model for Sjogren's syndrome. Rheumatology (Oxford, England), 48 (7). pp. 727-733.

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<h4>Objective</h4>To investigate a role for the inflammatory mediator, nitric oxide (NO) in SS, an autoimmune condition characterized by salivary and lacrimal gland hypofunction resulting from failure of acinar cells to secrete.<h4>Methods</h4>FURA-2 microfluorimetry was used to measure agonist-evoked changes of [Ca(2+)](i) in isolated mouse and human salivary acinar cells following exposure to NO donors.<h4>Results</h4>NO had a biphasic effect on salivary acinar function. Acute exposure to NO (2 min) caused a cyclic guanosine monophosphate (GMP)-dependent, 1-H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-sensitive increase in the Ca(2+) signal elicited in response to acetylcholine (ACh) stimulation, consistent with stimulation of ryanodine receptors by cyclic adenosine diphosphate ribose. Prolonged exposure to NO (>40 min) significantly reduced the ACh-evoked Ca(2+) signal by a mechanism independent of cyclic GMP. We found no differences between the responses of human and mouse acinar cells.<h4>Conclusion</h4>Our data show that chronic exposure to NO, which is known to be elevated in SS, could have a role in salivary gland hypofunction. We note a similarity in the response to stimulation of salivary acinar exposed to NO and that which we have previously reported in salivary acinar cells isolated from patients with SS. We speculate that NO-mediated nitrosylation of one or more elements of the signal transduction pathway could underlie down-regulation of salivary function in SS.

Item Type: Article
Additional Information: ## TULIP Type: Articles/Papers (Journal) ##
Uncontrolled Keywords: Submandibular Gland, Cells, Cultured, Animals, Mice, Inbred Strains, Humans, Mice, Sjogren's Syndrome, Calcium, Nitric Oxide, Acetylcholine, Nitroso Compounds, S-Nitroso-N-Acetylpenicillamine, Fura-2, Nitric Oxide Donors, Fluorometry, Models, Animal, Signal Transduction, Male
Subjects: ?? RK ??
Divisions: Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences > School of Dentistry
Depositing User: Symplectic Admin
Date Deposited: 16 Oct 2009 09:18
Last Modified: 15 Mar 2024 07:42
DOI: 10.1093/rheumatology/kep100
Publisher's Statement : This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Rheumatology following peer review. The definitive publisher-authenticated version (Vicky L. Caulfield , Colette Balmer , Luke J. Dawson , and Peter M. Smith A role for nitric oxide-mediated glandular hypofunction in a non-apoptotic model for Sjögren's syndrome Rheumatology Advance Access published on July 1, 2009, DOI 10.1093/rheumatology/kep100. Rheumatology 48: 727-733) is available online at: http://dx.doi.org/10.1093/rheumatology/kep100
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URI: https://livrepository.liverpool.ac.uk/id/eprint/1166