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Parasympathetic Modulation of Local Acute Inflammation in Murine Submandibular Glands


The parasympathetic nervous system controls submandibular glands (SMG) functions in physiological and pathological conditions via muscarinic acetylcholine receptors (mAchR). We had previously demonstrated that IFNγ and carbachol stimulate amylase secretion in normal murine SMG by mAchR activation. While the cytokine action depended on nitric oxide synthase activation, the effect of the agonist was mediated by prostaglandin E2 (PGE2) production. Both IFNγ and carbachol triggered IFNγ secretion in SMG. We here show that during local acute inflammation (LAI) induced by intraglandular injection of bacterial endotoxin, lypopolisaccharide (LPS), amylase secretion is decreased in comparison to control glands. We also observed that the muscarinic agonist carbachol stimulates in a dose-dependent manner amylase activity by M2 and M3 mAchR activation. Moreover, cyclooxygenase-2 (COX-2) activation and subsequent PGE2 liberation, in a nitric oxide independent manner, seem to be involved in M3 and M2 receptor activation by carbachol. In contrast, the addition of exogenous IFNγ or carbachol inhibits the cytokine liberation in LAI glands.

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  1. 1.

    Emmelin, N. 1987. Nerve interactions in salivary glands. J. Dent. Res. 66:509–517.

    Google Scholar 

  2. 2.

    Castle, D., and A. Castle. 1998. Intracellular transport and secretion of salivary proteins. Crit. Rev. Oral. Biol. Med. 9:4–22.

    Google Scholar 

  3. 3.

    Zhang, W., A. Fukushi, J. Nishiyama, N. Wada, and N. Kamimurra. 1996. Role of extracellular calcium in acetylcholine-induced repetitive calcium release in submandibular acinar cells of rat. J. Cell. Physiol. 167:277–284.

    Google Scholar 

  4. 4.

    Sterin-Borda, L., E. Borda, M. E. Sales, M. Rodríguez, M. M. E. de Bracco. 1996. Induction of ileum muscarinic cholinoceptors signal transduction pathways by rat interferon gamma. Int. J. Immunopharmacol. 18:17–22.

    Google Scholar 

  5. 5.

    Español, A. J. and M. E. Sales. 2001. Parasympathetic modulation of amylase secretion by IFNγ in murine submandibular glands. Int. Immunopharmacol. 1:903–910.

    Google Scholar 

  6. 6.

    Bernfeld, P. 1955. Amylases α and β. Methods Enzymol. 149–158

  7. 7.

    Lowry, O., N. Rosebrough, R. Randall, and A. Farr. 1971. Protein measurement with Folin phenol reagents. J. Biol. Chem. 193:265–268.

    Google Scholar 

  8. 8.

    Shiozaki, K., E. Iseki, H. Uchiyama, Y. Watanabe, T. Haga, K. Kameyama, T. Ikeda, T. Yamamoto, and K. Kosaka. 1999. Alterations of muscarinic acetylcholine receptor subtypes in diffuse Lewy body. J. Neurol. Neurosurg. Psychiatry. 67:209–213.

    Google Scholar 

  9. 9.

    Bredt, S. and S. H. Snyder. 1989. Nitric oxide mediates glutamate linked enhancement of cGMP levels in cerebellum. Proc. Natl. Acad. Sci. U.S.A. 86:9000–9030.

    Google Scholar 

  10. 10.

    Granstrom, E. and H. Kindhal. 1978. Radioimmunoassay of prostaglandins and Thromboxanes research. In: J. C. Folich ed. Advances in Prostaglandin and Thromboxune Research, Raven press, New York, pp. 119–210.

    Google Scholar 

  11. 11.

    Lopez-Urrutia, L., A. Alonso, V. Bayon, M. L. Nieto, A. Orduna, and M. Sanchez Crespo. 2001. Brucella lipopolysaccharides induce cyclooxygenase-2 expression in monocytic cells. Biochem. Biophys. Res. Commun. 30:289–292.

    Google Scholar 

  12. 12.

    Liaudet, L., J. G. Mabley, P. Pacher, L. Virag, F. G. Soriano, A. Marton, G. Hasko, F. A. Deitch, and C. Szabo. 2002. Inosine exerts a broad range of anti-inflammatory effects in a murine model of acute lung injury. Ann. Surg. 235:568–578.

    Google Scholar 

  13. 13.

    Wolber, E. M., J. Fandrey, U. Frackowski, and W. Jelkmann. 2001. Hepatic thrombopoietin mRNA is increased in acute inflammation. Thromb. Haemost. 86:1421–1424.

    Google Scholar 

  14. 14.

    Jain, N. K., C. S. Patil, S. K. Kulkarni, and A. Singh. 2002. Modulatory role of cyclooxygenase inhibitors in aging-and scopolamine or lipopolysaccharide-induced cognitive dysfunction in mice. Behav. Brain Res. 132:369–376.

    Google Scholar 

  15. 15.

    Lomniczi, A., C. Mohn, A. Faletti, A. Franchi, S. M. McCann, V. Rettori, and J. C. Elverdin. 2001. Inhibition of salivary secretion by lipopolysaccharide possible role of prostaglandins. Am. J. Physiol. Endocrinol. Metab. 281: E405-E411.

    Google Scholar 

  16. 16.

    Maier, J. A., D. Morelli, and A. Balsari. 1995. The differential response to interferon gamma by normal and transformed endothelial cells. Biochem. Biophys. Res. Commun. 214:582–588.

    Google Scholar 

  17. 17.

    Kile, B. T. and W. S. Alexander. 2001. The suppressors of cytokine signaling (SOCS). Life Sci. 58:1627–1635.

    Google Scholar 

  18. 18.

    Colasanti, M., E. Cavalieri, T. Persichinni, V. Mollace, S. Mariotto, H. Suzuky, and G. Lauro. 1997. Bacterial lipopolysaccharide plus IFNγ elicit very fast inhibition of a Ca2+ dependent nitric oxide synthase activity in human astrocytoma cells. J. Biol. Chem. 272:7582–7585.

    Google Scholar 

  19. 19.

    Pesquero, J. B., J. L. Pesquero, S. M. Oliveira, A. A. Roscher, R. Metzger, D. Ganten, and M. Bader, 1996. Molecular cloning and functional characterization of a mouse bradykinin B1 receptor gene. Biochem. Biophys. Res. Commun. 220:219–225.

    Google Scholar 

  20. 20.

    Mitchell, J. A. and T. W. Evans. 1998. Cyclooxygenase-2 as a therapeutic target. Inflamm. Res. 47: S88-S92.

    Google Scholar 

  21. 21.

    Quissell, D. O. 1992. Signal transduction mechanisms involved in salivary gland regulated exocytosis. Crit. Rev. Oral. Biol. Med. 3:83–107.

    Google Scholar 

  22. 22.

    Caulfield, M. P. and N. J. M. Birdsall. 1998. International Union of Pharmacology. XVII. Classification of Muscarinic acetylcholine receptors. Pharmacol. Rev. 50:279–286.

    Google Scholar 

  23. 23.

    Jeremy, J. Y., D. P. Mikhailidis, and P. Dandona. 1986. Prostanoid synthesis by the rat urinary bladder: Evidence for stimulation through muscarinic receptor-linked calcium channels. Naunyn Schmiedebergs Arch. Pharmacol. 334:463–467.

    Google Scholar 

  24. 24.

    Felder, C. C. 1995. Muscarinic acetylcholine receptors: Signal transduction through multiple effectors. FASEB J. 9:619–625.

    Google Scholar 

  25. 25.

    Esquifino, A. I., P. O. Castrillon, A. Arce, R. A. Cutrera, and D. P. Cardinali. 2001. Effect of parasympathetic decentralization on interferon-gamma release from rat submandibular lymph nodes in vitro. Auton. Neurosci. 91:10–15.

    Google Scholar 

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Correspondence to María Elena Sales.

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Español, A.J., de la Torre, E. & Sales, M.E. Parasympathetic Modulation of Local Acute Inflammation in Murine Submandibular Glands. Inflammation 27, 97–105 (2003).

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  • murine submandibular glands
  • inflammation, interferonγ
  • muscarinic acetylcholine receptors
  • COX-2
  • prostaglandin E2