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The adenosine A2a receptor is up-regulated in the lacrimal glands of NOD mice, an experimental model of Sjögren's syndrome
Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
Department of Pharmacology and Pharmaceutical Sciences, University of Southern California.
Department of Pharmacology and Pharmaceutical Sciences, University of Southern California.
Department of Pharmacology and Pharmaceutical Sciences, University of Southern California.
Vise andre og tillknytning
(engelsk)Manuskript (preprint) (Annet vitenskapelig)
Identifikatorer
URN: urn:nbn:se:lnu:diva-13662OAI: oai:DiVA.org:lnu-13662DiVA, id: diva2:432886
Tilgjengelig fra: 2011-08-08 Laget: 2011-08-08 Sist oppdatert: 2012-01-03bibliografisk kontrollert
Inngår i avhandling
1. Effects of adenosine and acetylcholine on the lacrimal gland
Åpne denne publikasjonen i ny fane eller vindu >>Effects of adenosine and acetylcholine on the lacrimal gland
2011 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Alternativ tittel[sv]
Effekter av adenosin och acetylkolin på tårkörteln
Abstract [en]

A balanced tear film is essential for a healthy ocular surface. Insufficient tear production may result in dry eye, a common disorder in the elderly population. Dry eye causes significant discomfort in the patients and may lead to visual impairment and ocular infections. The lacrimal gland secretes water, proteins and electrolytes to the aqueous layer of the tear film. Lacrimal gland secretion is tightly regulated by e.g. neuronally released acetylcholine. The effect of acetylcholine on lacrimal gland secretion was recently found to be potentiated by adenosine. Adenosine is an important signaling molecule acting upon the adenosine receptors: A1, A2A, A2B and A3.

The aim of this thesis was to study effects of adenosine and acetylcholine on intracellular signaling pathways and lacrimal gland secretion. Cholinergic stimulation of secretion was shown to be regulated by the mitogen activated protein kinase p38, a protein previously not known to be involved in exocrine secretion. p38 was activated in response to cholinergic stimulation and inhibition of p38 significantly diminished cholinergic secretion.

When investigating adenosine effects, potentiation of cholinergic secretion was observed by activation of the A2B receptor in addition to the previously studied A1 receptor. An A2 receptor agonist increased cholinergic rabbit lacrimal gland protein secretion at several concentrations. The increase was inhibited by antagonism of the A2B receptor, but not the A2A receptor. When investigating the intracellular signaling pathways following adenosine and acetylcholine receptor activation, adenosine was shown to increase of cAMP levels. An additional increase in cAMP levels was observed after parallel adenosine and cholinergic receptor activation. Inhibition of Ca2+ release from the endoplasmic reticulum had inhibitory effects of cholinergic stimulation of secretion. In addition, the expression of adenosine receptors in a mouse model of autoimmune dry eye was investigated. The results showed a lymphocyte dependent upregulation of A2A receptors in diseased mice compared to controls.

In conclusion, the results in this thesis provide significant contributions in the search of dry eye therapeutics through studies of adenosine and acetylcholine receptor activation.

sted, utgiver, år, opplag, sider
Växjö, Kalmar: Linnaeus Univeristy Press, 2011. s. 76
Serie
Linnaeus University Dissertations ; 59/2011
Emneord
Lacrimal gland, adenosine, adenosine receptors, signal transduction, exocrine secretion, tear film, dry eye, Sjögren’s syndrome, acetylcholine, mitogen activated protein kinase, p38
HSV kategori
Forskningsprogram
Naturvetenskap, Biomedicinsk vetenskap
Identifikatorer
urn:nbn:se:lnu:diva-13636 (URN)978-91-86491-97-0 (ISBN)
Disputas
2011-09-09, Sal N2007, Smålandsgatan 26B, Kalmar, 09:30 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2011-08-09 Laget: 2011-08-01 Sist oppdatert: 2018-01-12bibliografisk kontrollert

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