RESUMEN
Nitric oxide mediates esophageal peristalsis and lower esophageal sphincter (LES) relaxation. Superoxide produced with inflammation inactivates nitric oxide. Superoxide is cleared in biological systems by superoxide dismutase. We tested the hypothesis that superoxide and the superoxide scavenging system modulate LES function. Transverse strips of muscle from the opossum LES relaxed when stimulated by an electrical field. Diethyldithiocarbamite was used to inhibit copper/zinc superoxide dismutase. Xanthine and xanthine oxidase were used to generate superoxide. Xanthine with xanthine oxidase or diethyldithiocarbamite alone had no effect on the LES. However, xanthine/xanthine oxidase and diethyldithiocarbamite reduced LES relaxation 34.1% and increased its resting tone 71.2%. Superoxide dismutase did not affect LES function, but protected the tissue from the effects of diethyldithiocarbamite and xanthine/xanthine oxidase. These studies are consistent with the hypothesis that superoxide acts by inactivating nitric oxide and suggest that these antioxidant enzyme systems may play a role in the maintenance of LES function.
Asunto(s)
Unión Esofagogástrica/fisiología , Depuradores de Radicales Libres/metabolismo , Zarigüeyas/fisiología , Superóxido Dismutasa/fisiología , Superóxidos/metabolismo , Animales , Ditiocarba/farmacología , Relación Dosis-Respuesta a Droga , Estimulación Eléctrica , Unión Esofagogástrica/efectos de los fármacos , Femenino , Radicales Libres/metabolismo , Técnicas In Vitro , Masculino , Relajación Muscular/efectos de los fármacos , Relajación Muscular/fisiología , Tono Muscular/efectos de los fármacos , Tono Muscular/fisiología , Superóxido Dismutasa/antagonistas & inhibidores , Superóxido Dismutasa/efectos de los fármacos , Xantina , Xantina Oxidasa/farmacología , Xantinas/farmacologíaRESUMEN
Superoxide radical (O2-.) combines with nitric oxide (NO) to form peroxynitrite, thereby nullifying the biological activity of NO. Superoxide dismutase (SOD) prevents this reaction by converting O2-. to H2O2. We tested the hypotheses that the antioxidant enzymes catalase (CAT), Mn SOD, and Cu/Zn SOD are present in enteric neurons of the opossum esophagus, and that O2-. alters esophageal motor function. Immunostaining demonstrated CAT, Mn SOD, and Cu/Zn SOD immunoreactivity in interganglionic nerve bundles and ganglia of the myenteric and submucosal plexuses. Western blot analysis confirmed the presence of these enzymes in homogenates of esophageal muscularis propria, and enzyme assays demonstrated Cu/Zn SOD and Mn SOD activities of 262 and 73 U/mg protein, respectively. Both diethyldithiocarbamic acid, an inhibitor of Cu/Zn SOD, and xanthine (X) with xanthine oxidase (XO), which generate O2-., shortened the latency of the nerve-mediated contraction of circular esophageal muscle, the off response, by 20.2 and 23.4%, respectively. SOD alone did not affect the latency, but it inhibited the effect of X with XO on the latency. Antioxidant enzymes found in intramural esophageal nerves may play a role in regulating NO-mediated neuromuscular communication in the esophagus.
Asunto(s)
Catalasa/metabolismo , Esófago/inervación , Sistema Nervioso/metabolismo , Superóxido Dismutasa/fisiología , Animales , Western Blotting , Esófago/fisiología , Femenino , Ganglios/metabolismo , Inmunohistoquímica/métodos , Masculino , Plexo Mientérico/metabolismo , Zarigüeyas , Especies Reactivas de Oxígeno/metabolismo , Coloración y EtiquetadoRESUMEN
The present study investigated changes in small intestinal epithelial transport in rabbits infected with rotavirus. The crypt depth-villus height ratio was increased in infected ileal tissue as a result of a significant increase in crypt depth and patchy shortening of the villi. Similar villus damage was seen in the jejunum. Despite these histological changes, basal fluid absorption by both the ileum and jejunum of infected animals was unaltered. Values for basal short-circuit current and resistance were similar; however, the increase in short-circuit current evoked by prostaglandin E2 was significantly smaller in rotavirus-infected tissues than in controls. The apparent Vmax for electrogenic glucose and alanine uptake by the jejunum was significantly increased following inoculation with rotavirus. Reduced responsiveness to the secretory effect of prostaglandin E2 and increased nutrient uptake may limit diarrhea that would otherwise be expected to occur as a result of the changes in mucosal architecture. This has important implications on the clinical treatment of rotavirus diarrhea, suggesting that oral rehydration therapy, which depends on the active transport of nutrients, may provide a more effective treatment than the use of cyclooxygenase inhibitors.