Activation of nitric oxide signaling through muscarinic receptors in submandibular glands by primary Sjogren syndrome antibodies

Primary Sjogren Syndrome is a chronic autoimmune disease characterized by e xocrine gland dysfunction. Here we present evidence of the activation of ni tric oxide signaling cascade by circulating antibodies of patients with Sjo gren Syndrome in rat submandibular glands. Constitutive nitric oxide syntha se and cyclic GMP levels are modulated by Sjogren IgGs through the activati on of muscarinic acetylcholine receptors on the glands. The effects are sim ilar to those produced by the agonist carbachol and blocked by the antagoni st atropine. The involvement of M-1 subtype of muscarinic receptors is prop osed since both a synthetic peptide homologous to an extracellular domain o f M-1 receptor and pirenzepine, a selective M-1 antagonist, partially block ed the effects. We conclude that Sjogren Syndrome antibodies can activate n itric oxide signaling in submandibular glands by interacting with muscarini c acetylcholine receptors. (C) 1999 Academic Press.