Benefits of long-term pilocarpine due to increased muscarinic acetylcholine receptor 3 in salivary glands

Hypofunction of the salivary gland causes several life-disrupting side effects such as dental caries, oral candidiasis, loss of taste, and swallowing disorders. No satisfactory therapy has been established to treat salivary hypofunction. Pilocarpine represents a potential treatment for dry mouth due to Sjogren's syndrome (SS). Although subjective improvement was consistently observed with pilocarpine therapy, the mechanism was unclear. In this study, we investigated the mechanism of recovery in salivation following treatment with pilocarpine. We first examined the effectiveness of pilocarpine in SS patients as quantified by the Saxon test and the visual analogue scale average. We found that salivation ability and subjective symptoms improved by continuous administration of pilocarpine. These results demonstrated that long-term medication for dry mouth patients was more effective. However, as the mechanism remained unclear, molecular biological mechanisms were analyzed based on the effects of continuous administration of pilocarpine using model mice. In the molecular biological analysis, continuous administration of pilocarpine was effective in both ICR and SS model mice. Gene and protein expression of muscarinic acetylcholine receptor 3 (M3R) increased in salivary glands following continuous administration of pilocarpine compared with single administration. Therefore, continuous administration of pilocarpine effectively induced M3R expression, thereby activating salivation.