Role of the epithelium in the control of intestinal motility: implications for intestinal damage after anoxia and reoxygenation.
A vibration technique was used to dislocate the epithelium from the rat small intestine, in order to study the possible regulatory role of the epithelium on intestinal motility. Complete removal of the epithelium led to a slightly potentiated contraction of the longitudinal smooth muscle by the muscarinic agonist methacholine (pD2. 6.5 +/- 0.1 vs. 6.2 +/- 0.2). The maximal beta-adrenergic response expressed relative to the relaxation by 0.5 mM dibutyryl cyclic AMP increased from 55.9 +/- 9.0% to 72.6 +/- 9.1% by this treatment. Efforts were made to relate these observations to the endothelium-dependent relaxation in blood vessels, but no indication was found for a similar mechanism in the small intestine. Not only mechanical dislocation can be employed to affect the mucosal layer, but also intestinal ischemia has been reported to lead to mucosal damage. In this study we mimicked ischemia by applying in vitro anoxia and subsequent reoxygenation to isolated intestinal segments. When intestinal segments are isolated and kept in physiological buffer, xanthine dehydrogenase is converted slowly to xanthine oxidase, irrespective of whether the buffer is oxygenated or not. No evidence was found for oxygen radical damage after anoxia and reoxygenation. However, the intestinal mucosa was damaged both after normoxia, and after anoxia and reoxygenation. Anoxia and subsequent reoxygenation did not affect muscarinic contraction, but slightly increased the beta-adrenergic relaxation, which partly correlates with the effects of mechanical dislocation of the epithelium. The increased sensitivity of the smooth muscle after epithelial damage might be involved in motility changes during intestinal inflammatory diseases.
Van der Vliet
A
A
Department of Pharmacochemistry, Faculty of Chemistry, Vrije Universiteit, Amsterdam, The Netherlands.
Tuinstra
T J
TJ
Rademaker
B
B
Bast
A
A
D000818:Animals; D004848:Epithelium / Q000033:anatomy & histology / Q000502:physiology; D005769:Gastrointestinal Motility / Q000502:physiology*; D006861:Hydrogen Peroxide; D000860:Hypoxia / Q000473:pathology*; D007410:Intestinal Diseases / Q000473:pathology*; D007413:Intestinal Mucosa / Q000033:anatomy & histology / Q000502:physiology*; D007421:Intestine, Small / Q000473:pathology / Q000502:physiology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000503:physiopathology; D014732:Vibration / Q000009:adverse effects; D014969:Xanthine Oxidase / Q000378:metabolism
D006861:Hydrogen Peroxide; D014969:Xanthine Oxidase