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Am J Physiol Gastrointest Liver Physiol 275: G1333-G1340, 1998;
0193-1857/98 $5.00
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Vol. 275, Issue 6, G1333-G1340, December 1998

Ionizing radiation stimulates muscarinic regulation of rat intestinal mucosal function

F. Lebrun, A. Francois, M. Vergnet, L. Lebaron-Jacobs, P. Gourmelon, and N. M. Griffiths

Institut de Protection et de Sûreté Nucléaire, Département de Protection de la Santé de l'Homme et de Dosimétrie, Section Autonome de Radiobiologie Appliquée à la Médecine, F-92265 Fontenay-aux-Roses Cedex, France

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 (Isc) and transepithelial conductance (Gt) of stripped ileum were determined in Ussing chambers. Muscarinic receptor characteristics using the muscarinic antagonist [3H]quinuclidinyl benzilate and three unlabeled antagonists were measured in small intestinal plasma membranes together with two marker enzyme activities (sucrase, Na+-K+-ATPase). Enzyme activities were decreased 4 days after irradiation (day 4). Basal electrical parameters were unchanged. Maximal carbachol-induced changes in Isc and Gt were increased at day 4 (maximal Delta Isc = 195.8 ± 14.7 µA/cm2, n = 19, vs. 115.4 ± 8.2 µA/cm2, n = 63, for control rats) and unchanged at day 7. Dissociation 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 change in binding site number. Thus total body irradiation induces a temporary stimulation of cholinergic regulation of mucosal intestinal function that may result in radiation-induced diarrhea.

muscarinic receptor; short-circuit current; rat ileum


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