Parasympathetic modulation of amylase secretion by IFN gamma in murine submandibular glands

IFN gamma is a pleiotropic cytokine that exerts immunologic and non-immunol ogic functions. We show here that at low doses (10 U/ml). it stimulates amy lase secretion in murine submandibular glands (SMG) "via" muscarinic recept or activation. comparable to that produced by the muscarinic agonist carbac hol. Both effects are blocked by atropine, N-G-monomethyl-arginine (L-NMMA) and EGTA inhibited the cytokine effect on amylase secretion, involving the participation of a calcium-dependent isoform of nitric oxide synthase (NOS ). We confirm NOS activation because IFN gamma stimulates nitrite productio n and enzyme activity in SMG. Carbachol (10(-7) M)did not modify basal nitr ic oxide production. In addition, both IFN gamma and carbachol increase pro staglandin E, production in SMG, but while indomethacin potentiates IFN gam ma effect on amylase secretion, it blunted amylase secretion exerted by car bachol. Thus, IFN gamma and carbachol stimulate IFN gamma secretion on SMG in a dose-dependent manner. Our results are pointing to neuroregulatory fun ctions of IFN gamma in murine SMC, because it regulates its own levels in o ral cavity, perhaps to exert a local immuno-surveillance. 2001 Elsevier Sci ence B.V. All rights reserved.