MUSCARINIC RECEPTOR STIMULATION INCREASES TOLERANCE OF RAT SALIVARY-GLAND FUNCTION TO RADIATION-DAMAGE

Purpose: To investigate if muscarinic receptor-stimulated activation o f 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 collect ed 4-days before and 1-30 days after irradiation. Lag phase, flow rate , amylase secretion, and salivary sodium and potassium concentration w ere measured. Results: Pretreatment with pilocarpine or methacholine r esulted in an improvement of all measured functions of both glands. Pr etreatment with reserpine had no effect on parotid gland function. Res erpine plus methacholine did not increase parotid gland function when compared with methacholine alone, indicating a purely muscarinic recep tor stimulation as the initiator for the induced radioprotection. Pret reatment protective effects on submandibular gland function of reserpi ne plus methacholine were additive, indicating cooperation of muscarin ic and alpha-adrenergic receptors. Atropine pretreatment slightly incr eased the radiation induced loss of salivary gland function. Conclusio ns: Preirradiation activation of PLC/PIP2 second messenger pathway thr ough stimulation of muscarinic receptors reduces the salivary gland ra diosensitivity. The observed protection of salivary gland function may be of a secondary nature, implicating a cell conditioning after recep tor stimulation of the PLC/PIP2 pathway.