title: Ionizing radiation stimulates muscarinic regulation of rat intestinal mucosal function.
abstract: 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 DeltaIsc = 195.8 +/- 14.7 microA/cm2, n = 19, vs. 115.4 +/- 8.2 microA/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.
authors.affiliation: 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.
authors.forename: F
authors.initials: F
authors.lastname: Lebrun
authors.forename: A
authors.initials: A
authors.lastname: Francois
authors.forename: M
authors.initials: M
authors.lastname: Vergnet
authors.forename: L
authors.initials: L
authors.lastname: Lebaron-Jacobs
authors.forename: P
authors.initials: P
authors.lastname: Gourmelon
authors.forename: N M
authors.initials: NM
authors.lastname: Griffiths
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D004553:Electric Conductivity; D004798:Enzymes / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000502:physiology* / Q000528:radiation effects*; D007421:Intestine, Small / Q000378:metabolism / Q000502:physiology* / Q000528:radiation effects*; D008297:Male; D009116:Muscarine / Q000378:metabolism*; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000378:metabolism / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000378:metabolism
chemical_list: D004798:Enzymes; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D011813:Quinuclidinyl Benzilate; D009116:Muscarine; D002217:Carbachol