Background: We wanted to determine (via an immunopharmacological approach) whether the c-Jun NH<sub>2</sub> terminal kinase (JNK) cascade is phosphorylated in the submandibular gland by carbachol and cholinergic autoantibodies (IgG) present in the sera of patients with primary Sjögren’s syndrome (pSS) by interaction and activation of salivary gland muscarinic acetylcholine receptors (mAChRs). Methods: The JNK, PGE<sub>2</sub> and NOS assays were measured in rat sub- mandibular gland with pSS IgG and carbachol alone or in the presence of different blocker agents. Results: pSS IgG- activated M<sub>3</sub> mAChRs stimulated JNK phosphorylation whereas the activation of M<sub>1</sub> mAChRs by carbachol stimulated JNK phosphorylation involving calcium-activated mechanism. The intracellular pathway leading to pSS IgG-induced biological effects on JNK activity involved activation of protein kinase C (PKC), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) enzymes. Also, activation of COX-2 and COX-1 by pSS IgG and carbachol-induced PGE<sub>2</sub> generation were involved. Conclusion: These results may contribute to better understanding the modulatory role of JNK enzymes by cholinergic autoantibodies from pSS patients acting on mAChR in rat submandibular gland.
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