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.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Emmelin, N. 1987. Nerve interactions in salivary glands. J. Dent. Res. 66:509–517.
Castle, D., and A. Castle. 1998. Intracellular transport and secretion of salivary proteins. Crit. Rev. Oral. Biol. Med. 9:4–22.
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.
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.
Español, A. J. and M. E. Sales. 2001. Parasympathetic modulation of amylase secretion by IFNγ in murine submandibular glands. Int. Immunopharmacol. 1:903–910.
Bernfeld, P. 1955. Amylases α and β. Methods Enzymol. 149–158
Lowry, O., N. Rosebrough, R. Randall, and A. Farr. 1971. Protein measurement with Folin phenol reagents. J. Biol. Chem. 193:265–268.
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.
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.
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.
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.
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.
Wolber, E. M., J. Fandrey, U. Frackowski, and W. Jelkmann. 2001. Hepatic thrombopoietin mRNA is increased in acute inflammation. Thromb. Haemost. 86:1421–1424.
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.
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.
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.
Kile, B. T. and W. S. Alexander. 2001. The suppressors of cytokine signaling (SOCS). Life Sci. 58:1627–1635.
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.
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.
Mitchell, J. A. and T. W. Evans. 1998. Cyclooxygenase-2 as a therapeutic target. Inflamm. Res. 47: S88-S92.
Quissell, D. O. 1992. Signal transduction mechanisms involved in salivary gland regulated exocytosis. Crit. Rev. Oral. Biol. Med. 3:83–107.
Caulfield, M. P. and N. J. M. Birdsall. 1998. International Union of Pharmacology. XVII. Classification of Muscarinic acetylcholine receptors. Pharmacol. Rev. 50:279–286.
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.
Felder, C. C. 1995. Muscarinic acetylcholine receptors: Signal transduction through multiple effectors. FASEB J. 9:619–625.
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.
About this article
Cite this article
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). https://doi.org/10.1023/A:1023230717435
- murine submandibular glands
- inflammation, interferonγ
- muscarinic acetylcholine receptors
- prostaglandin E2