Impaired neurotransmitter release from lacrimal and salivary gland nerves of a murine model of Sjögren's syndrome.
OBJECTIVE
To determine whether lacrimal and salivary gland nerves of an animal model of Sjögren's syndrome, the MRL/lpr mouse, are able to release acetylcholine. The second purpose was to determine whether activation of the lacrimal gland nerves of the MRL/lpr mouse leads to protein secretion.


METHODS
Total saliva was collected for 10 minutes from the oral cavity of male and female MRL/lpr and MRL/+ mice, after intraperitoneal stimulation with pilocarpine and isoproterenol. Lacrimal and salivary gland lobules prepared from 18-week-old MRL/lpr and MRL/+ mice were incubated in the presence of depolarizing KCl (75 mM) solution. Acetylcholine release and peroxidase secretion (a protein secreted by the lacrimal gland) were measured using a spectrofluorometric assay.


RESULTS
Female, but not male, MRL/lpr mouse salivary glands were hyper-responsive to in vivo injection of secretagogues. These mice produced significantly higher amounts of saliva than did age-matched MRL/+ mice. Lacrimal and salivary gland nerves from 18-week-old MRL/+ mice released acetylcholine in response to a depolarizing KCl solution. In contrast, nerves in glands from 18-week-old MRL/lpr mice did not increase acetylcholine release in response to the depolarizing solution. Moreover, lacrimal glands from 18-week-old MRL/+ mice were able to secrete peroxidase in response to a depolarizing KCl solution, whereas those from 18-week-old MRL/lpr could not. This was not due to a defect in the secretory process, because addition of an exogenous secretagogue elicited peroxidase secretion from 18-week-old MRL/lpr as well as MRL/+ mice lacrimal glands.


CONCLUSIONS
The results show that activation of nerves of lacrimal and salivary glands infiltrated with lymphocytes does not increase the release of neurotransmitters, which results in impaired secretion from these glands.
Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA. zoukhri@vision.eri.harvard.edu
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D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002794:Choline / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007274:Injections, Intraperitoneal; D007545:Isoproterenol / Q000494:pharmacology; D007765:Lacrimal Apparatus / Q000187:drug effects / Q000294:innervation*; D008297:Male; D051379:Mice; D019463:Mice, Inbred MRL lpr; D010275:Parasympathetic Nervous System / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D010862:Pilocarpine / Q000494:pharmacology; D012463:Saliva / Q000378:metabolism; D012469:Salivary Glands / Q000187:drug effects / Q000294:innervation*; D012859:Sjogren's Syndrome / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013564:Sympathetic Nervous System / Q000378:metabolism*; D013666:Tears / Q000378:metabolism
D010862:Pilocarpine; D009195:Peroxidase; D007545:Isoproterenol; D002794:Choline; D000109:Acetylcholine