Muscarinic receptor stimulation increases tolerance of rat salivary gland function to radiation damage

Purpose: To investigate if muscarinic receptor-stimulated activation of the PLC/PIP2 second messenger pathway prior to irradiation increases the radiotolerance of rat salivary gland. Materials and methods: Rats were treated with pilocarpine, methacholine, reserpine, methacholine plus reserpine, or atropine prior to irradiation with a single dose of 15 Gy X-rays. Parotid and submandibular/sublingual saliva was collected 4-days before and 1-30 days after irradiation. Lag phase, flow rate, amylase secretion, and salivary sodium and potassium concentration were measured. Results: Pretreatment with pilocarpine or methacholine resulted in an improvement of all measured functions of both glands. Pretreatment with reserpine had no effect on parotid gland function. Reserpine plus methacholine did not increase parotid gland function when compared with methacholine alone, indicating a purely muscarinic receptor stimulation as the initiator for the induced radioprotection. Pretreatment protective effects on submandibular gland function of reserpine plus methacholine were additive, indicating cooperation of muscarinic and alpha-adrenergic receptors. Atropine pretreatment slightly increased the radiation induced loss of salivary gland function. Conclusions: Preirradiation activation of PLC/PIP2 second messenger pathway through stimulation of muscarinic receptors reduces the salivary gland radiosensitivity. The observed protection of salivary gland function may be of a secondary nature, implicating a cell conditioning after receptor stimulation of the PLC/PIP2 pathway