Activation of Nitric Oxide Signaling through Muscarinic Receptors in Submandibular Glands by Primary Sjِgren Syndrome Antibodies

Primary Sjِgren Syndrome is a chronic autoimmune disease characterized by exocrine gland dysfunction. Here we present evidence of the activation of nitric oxide signaling cascade by circulating antibodies of patients with Sjِgren Syndrome in rat submandibular glands. Constitutive nitric oxide synthase and cyclic GMP levels are modulated by Sjِgren IgGs through the activation of muscarinic acetylcholine receptors on the glands. The effects are similar to those produced by the agonist carbachol and blocked by the antagonist atropine. The involvement of M1subtype of muscarinic receptors is proposed since both a synthetic peptide homologous to an extracellular domain of M1receptor and pirenzepine, a selective M1antagonist, partially blocked the effects. We conclude that Sjِgren Syndrome antibodies can activate nitric oxide signaling in submandibular glands by interacting with muscarinic acetylcholine receptors.