Modification of rat intestinal muscarinic cholinergic receptors by ionizing radiation

Evidence exists for increased fluid and chloride secretion induced by ionizing radiation. Acetylcholine via stimulation of muscarinic epithelial receptors may be implicated in such increases. This study addresses the question of whether ionizing radiation modifies cholinergic muscarinic receptors. Male Wistar rats were exposed to total body gamma irradiation (8 Gy; 1.3 Gy.min-1; 60Co source). Plasma membranes were prepared from small intestinal mucosal scrapings and marker enzyme activities (sucrose, Na+/K+-ATPase) measured. Muscarinic receptor binding characteristics (Kd, Bmax) were determined using the non-selective muscarinic antagonist 3H-QNB (quinuclidinylbenzilate). Sucrase and Na+/K+-ATPase activities are maximally decreased 3 and 4 days (D3, D4) post irradiation (3 fold). Myeloperoxidase activity is markedly reduced (10 fold at D4) and is still lower than control values 21 days after irradiation (5 fold). Two 3H-QNB binding sites are observed for control rats. For the high affinity site, Kd is decreased up to 7 days after irradiation with a maximum at D4 (4 fold decrease) whereas Bmax is unchanged. For the low affinity binding site, both Kd and Bmax are reduced. The significance of these sites remains unclear. The increase of the affinity of the high affinity binding site is in agreement with an increased response to cholinergic stimulation, and so with increased fluid and chloride secretion. These results suggest a possible implication of a dysfunction of cholinergic regulation in irradiation-induced diarrhoea. Thus it is of interest to determine the mechanisms by which radiation can modify muscarinic mucosal receptors. (author)