Ionizing radiation stimulates muscarinic regulation of rat intestinal mucosal function

The aim of this study was to determine whether ionizing radiation modifies muscarinic regulation of intestinal mucosal function. Rats exposed to total body 8-Gy gamma-irradiation or sham irradiated were studied up to 21 days after irradiation. Basal and carbachol-stimulated short-circuit current (I- sc) and transepithelial conductance (G(t)) of stripped ileum were determine d in Ussing chambers. Muscarinic receptor characteristics using the muscari nic antagonist [H-3]quinuclidinyl benzilate and three unlabeled antagonists were measured in small intestinal plasma membranes together with two marke r enzyme activities (sucrase, Na+-K+-ATPase). Enzyme activities were decrea sed 4 days after irradiation (day 4). Basal electrical parameters were unch anged. Maximal carbachol-induced changes in I-sc and G(t) were increased at day 4 (maximal Delta I-sc = 195.8 +/- 14.7 mu A/cm(2), n = 19, vs. 115.4 /- 8.2 mu A/cm(2), n = 63, for control rats) and unchanged at day 7. Dissoc iation constant was decreased at day 4 (0.73 +/- 0.29 nM, n = 10, vs. 2.14 +/- 0.39 nM, n = 13, for control rats) but unchanged at day 7, without chan ge in binding site number. Thus total body irradiation induces a temporary stimulation of cholinergic regulation of mucosal intestinal function that m ay result in radiation-induced diarrhea.