Early radiation effects on muscarinic receptor-induced secretory responsiveness of the parotid gland in the freely moving rat

Although the salivary glands have a low rate of cell turnover, they are rel atively radiosensitive. To study the possible mechanism behind this inheren t radiosensitivity, a rat model was developed in which saliva can be collec ted after local irradiation of the parotid gland without the use of anesthe tics or stressful handling. Saliva secretion was induced by the partial mus carinic receptor agonist pilocarpine (0.033 mg/kg) with or without pretreat ment with the beta-adrenoceptor antagonist propranolol (2.5 mg/kg), or the full muscarinic receptor agonist methacholine (0.16-16 mg/min), and measure d during 5 min per drug dose before and 1, 3, 6 and 10 days after irradiati on. The maximal secretory response induced by pilocarpine plus propranolol was increased compared to that with pilocarpine alone but did not reach the level of methacholine-induced secretion, which was about five times higher . One day after irradiation a decrease in maximal pilocarpine-induced secre tion was observed (-22%) using the same dose of pilocarpine that induces 50 % of the maximal response (ED50), in both the absence and presence of propr anolol, indicating that the receptor-drug interaction was not affected by t he radiation at this time. The secretory response to methacholine 1 day aft er irradiation, however, was normal. At day 3 after irradiation, the maxima l methacholine-induced secretion was also affected, whereas pilocarpine (+/ -propranolol)-induced maximal secretion decreased further. At day 6 after i rradiation, maximal secretory responses had declined to approximately 50% r egardless of the agonist used, whereas ED50 values were still unaffected. N o net acinar cell loss was observed within the first 10 days after irradiat ion, and this therefore could not account for the loss in function. The res ults indicate that radiation does not affect cell number or receptor-drug i nteraction, but rather signal transduction, which eventually leads to the i mpaired response. We hypothesize that the early radiation effect, within 3 days, may be membrane damage affecting the receptor-G-protein signal transf er. Later critical damage, however, is probably of a different nature and m ay be located in the second-messenger signal transduction pathway downstrea m from the G protein, not necessarily involving cellular membranes. (C) 200 0 by Radiation Research Society.