We demonstrate that serum immunoglobulin G (IgG) directed against glandular M3 muscarinic acetylcholine receptors (M₃mAChR) and pilocarpine triggers the increment of superoxide dismutase (SOD) and catalase (CAT) and the production of nitric oxide (NO) and prostaglandin E₂(PGE₂).
Enzyme-linked immunosorbent assay (ELISA) was performed in the presence of the human M₂mAChR synthetic peptide as antigen to detect in serum of pSS patients the autoantibodies. Further, SOD and CAT specific activity and NO were determined chemically in the presence of anti-M₃mAChR IgG and pilocarpine. The level of PGE₂generation in the presence of autoantibody and pilocarpine was determined by ELISA.
An association between anti-M₂mAChR autoantibodies and pilocarpine given the increment of the specific activity of SOD and CAT in the serum of pSS patients and in the rat submandibular gland was observed. As a result of this action, M₃synthetic peptide and atropine abrogated the stimulatory action. The L-type calcium channel, calcium/calmodulin complex and COX-2 inhibitors selectively blocked the increment of the specific activity of SOD and CAT in the rat submandibular gland. An increased production of NO and PGE₂by the cholinergic autoantibody and pilocarpine was also detected.
On the basis of these results, the increment of the specific activity of SOD and CAT in pSS patients as compared to control healthy individuals may be seen as a defensive reaction to the increment of the amount of ROS, which becoming uncontrollable, leads to irreversible cellular and tissue damage.