Pérez Leirós C, Sterin-Borda L, Hubscher O, Arana R, Borda E S
Cátedra de Farmacología, Universidad de Buenos Aires y CEMIC, Buenos Aires, Argentina.
Clin Immunol. 1999 Feb;90(2):190-5. doi: 10.1006/clim.1998.4640.
Primary Sjögren 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 Sjögren Syndrome in rat submandibular glands. Constitutive nitric oxide synthase and cyclic GMP levels are modulated by Sjögren 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 M1 subtype of muscarinic receptors is proposed since both a synthetic peptide homologous to an extracellular domain of M1 receptor and pirenzepine, a selective M1 antagonist, partially blocked the effects. We conclude that Sjögren Syndrome antibodies can activate nitric oxide signaling in submandibular glands by interacting with muscarinic acetylcholine receptors.
原发性干燥综合征是一种以腺体外分泌功能障碍为特征的慢性自身免疫性疾病。在此，我们展示了干燥综合征患者循环抗体在大鼠颌下腺中激活一氧化氮信号级联反应的证据。组成型一氧化氮合酶和环磷酸鸟苷水平受干燥综合征免疫球蛋白G（IgGs）调节，通过激活腺体上的毒蕈碱型乙酰胆碱受体来实现。这些作用类似于激动剂卡巴胆碱所产生的作用，并被拮抗剂阿托品所阻断。由于与M1受体细胞外结构域同源的合成肽和选择性M1拮抗剂哌仑西平都能部分阻断这些作用，因此推测毒蕈碱受体M1亚型参与其中。我们得出结论，干燥综合征抗体可通过与毒蕈碱型乙酰胆碱受体相互作用来激活颌下腺中的一氧化氮信号。
