title: Low doses of ionizing radiation can prevent radiation-induced colonic epithelial hyporesponsiveness to muscarinic agonists.
abstract: OBJECTIVE
  Colonic epithelium hyporesponsiveness to different secretagogues occurs after exposure to ionizing radiation, increasing susceptibility to bacterial translocation and intraluminal toxins. Growing evidence suggests that the biological effects of radiation might be hormetic in nature. We investigated if exposure to low doses of ionizing radiation (LDR) can prevent colon hyposecretion due to subsequent larger doses.
  
  
  METHODS
  Rats were exposed to LDR (0.05 Gy) 24 h prior to 6 Gy, high dose radiation (HDR). The cyclic adenosine monophosphate (cAMP)-mediated pathway was explored using forskolin (FSK) and the intracellular Ca2+-mediated pathway through cholinergic stimulation. Changes in the colonic epithelium at the ultrastructural level were also explored.
  
  
  RESULTS
  Maximal short circuit current (Isc) response to carbachol was significantly reduced in the group exposed to 6 Gy HDR and this was completely prevented by prior exposure to LDR. Responses to both FSK and electrical field stimulation (EFS) were significantly reduced after HDR but they were not prevented by prior adaption of LDR. Hyposecretion was not prevented by the inducible nitric oxide synthase (iNOS) inhibitor L-N6-(l-iminoethyl)lysine (L-NIL) ruling out a role for iNOS-derived nitric oxide (NO) in the colonic hyposecretion associated with whole body radiation. Prior exposure to LDR diminished the deleterious effect of full HDR on the ultrastructure of colonic epithelium as colonocytes vacuolization, microvilli lost and separation between neighboring cells were less evident.
  
  
  CONCLUSIONS
  Previous exposure to LDR can prevent intracellular Ca2+-mediated colonic hyposecretion associated with exposure to HDR but fails to modify cAMP-mediated hyposecretion. Morphological damage at the ultrastructural level is less evident after prior LDR.
authors.affiliation: Intestinal Disease Research Program, Health Science Center, McMaster University, hamilton, Ontario, Canada. zaratenatalia1@yahoo.es
authors.forename: N
authors.initials: N
authors.lastname: Zarate
authors.forename: X Y
authors.initials: XY
authors.lastname: Wang
authors.forename: E J
authors.initials: EJ
authors.lastname: White
authors.forename: D
authors.initials: D
authors.lastname: Boreham
authors.forename: P K
authors.initials: PK
authors.lastname: Rangachari
authors.forename: J D
authors.initials: JD
authors.lastname: Huizinga
mesh_terms: D000818:Animals; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005768:Gastrointestinal Hormones / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects*; D008297:Male; D018721:Muscarinic Agonists / Q000008:administration & dosage*; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000528:radiation effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D005768:Gastrointestinal Hormones; D018721:Muscarinic Agonists