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  • 1.
    Carlsson, Stina K.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Effects of adenosine and acetylcholine on the lacrimal gland2011Doctoral thesis, comprehensive summary (Other academic)
    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.

  • 2.
    Carlsson, Stina K.
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Edman, Maria C.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Hamm-Alvarez, Sarah F.
    Department of Pharmacology and Pharmaceutical Sciences, University of Southern California.
    Gierow, J. Peter
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Intracellular events following adenosine and carbachol stimulation of rabbit lacrimal gland secretionManuscript (preprint) (Other academic)
  • 3.
    Carlsson, Stina K.
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Edman, Maria
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Delbro, Dick
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Gierow, Peter
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Adenosine A2 receptor presence, and synergy with cholinergic stimulation in rabbit lacrimal gland2010In: Current Eye Research, ISSN 0271-3683, E-ISSN 1460-2202, Vol. 35, no 6, p. 466-474Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Secretion from the lacrimal gland is an important part of the well-being of the eye, and a central part in the search for treatment of dry eye syndrome. Adenosine has stimulatory effects on the lacrimal gland, and can potentiate the effect of the cholinergic agonist carbachol (Cch). The aim of the present study is to investigate the presence of the adenosine A(2) receptor subtypes A(2A) and A(2B) in the rabbit lacrimal gland, and to characterize their role in regulated acinar cell secretion.

    METHODS: Expression of the receptors was investigated using reverse transcriptase-PCR (RT-PCR) and immunofluorescence, and secretion effects were studied using a secretion assay in isolated lacrimal gland acinar cells.

    RESULTS: Presence of both receptors was detected by RT-PCR and immunofluorescence. The secretion assay revealed a minor effect of stimulation of the A(2) receptors, and a strong synergistic effect with the cholinergic agonist Cch. The synergistic effect was significantly reduced by the A(2B) antagonist PSB 1115, but not by the A(2A) antagonist SCH 58261, indicating that A(2B) is the receptor responsible for this potentiation.

    CONCLUSIONS: The study reveals the presence of the adenosine A(2) receptor subtypes as well as a role for them in lacrimal gland secretion, and especially in the synergy with purinergic and cholinergic stimulation.

  • 4.
    Carlsson, Stina K.
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Gierow, J. Peter
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    p38 mitogen activated protein kinase regulates exocrine secretion in rabbit lacrimal gland.Manuscript (preprint) (Other academic)
  • 5.
    Carlsson, Stina K.
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Gierow, Peter
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    p38 mitogen-activated protein kinase modulates exocrine secretion in rabbit lacrimal gland2012In: Cellular & Molecular Biology Letters (Druk), ISSN 1425-8153, E-ISSN 1689-1392, Vol. 17, no 1, p. 1-10Article in journal (Refereed)
    Abstract [en]

    The lacrimal gland (LG) is an exocrine gland important for secretion of the tear film. The kinase p38 has important signal transduction functions, e.g. in gene transcription, but has previously not been known to modulate exocrine secretion. The aim of the current study was to investigate the role of p38 in carbachol (Cch)-induced LG secretion in LG acinar cells in vitro. Western blotting was used to determine the phosphorylation status of p38 and p42/44 and determine expression of p38 isoforms. To determine the effect of p38 inhibition on LG secretion, PD 169316, a general p38 inhibitor, and SB 239063, an inhibitor of p38α and β, were added to the cells prior to secretion measurements. The results revealed activation of p38 mediated by Cch stimulation and inhibition of Cch-induced secretion as a result of p38 inhibition. The inhibition was observed with PD 169316 isoforms, but not with SB 239063. The p38δ isoform was shown to have robust expression both by Western blotting of acinar cells and immunofluorescence of the whole gland. In conclusion, p38 activation mediates secretion in cholinergic stimulation of rabbit LG cells.

  • 6.
    Carlsson, Stina K.
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Wu, Kaijin
    Department of Pharmacology and Pharmaceutical Sciences, University of Southern California.
    Diaz, Daniel
    Department of Pharmacology and Pharmaceutical Sciences, University of Southern California.
    Hamm-Alvarez, Sarah F.
    Department of Pharmacology and Pharmaceutical Sciences, University of Southern California.
    Gierow, J. Peter
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    The adenosine A2a receptor is up-regulated in the lacrimal glands of NOD mice, an experimental model of Sjögren's syndromeManuscript (preprint) (Other academic)
1 - 6 of 6
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