Mayol Julio M, Adame-Navarrete Yolanda, Alarma-Estrany Pilar, Molina-Roldan Elena, Huete-Toral Fernando, Fernandez-Represa Jesus A
Servicio de Cirugia I (3(a) N), Hospital Clinico San Carlos, Universidad Complutense de Madrid, Madrid 28040, Spain.
World J Gastroenterol. 2006 Sep 14;12(34):5523-7. doi: 10.3748/wjg.v12.i34.5523.
To investigate the effects of luminal exposure to H2O(2) and two related thiol oxidizing agents on basal and stimulated chloride secretion in native colon using electrophysiological and pharmacological approaches.
Unstripped rat distal colon segments were mounted in Ussing chambers. Potential difference, calculated resistance and short-circuit current across unstripped colon segments were monitored with a dual voltage/current clamp. Paracellular permeability was assessed by measuring the mucosa-to-serosa flux of a fluorescent probe (FITC).
Luminal exposure to hydrogen peroxide transitorily stimulated chloride secretion without altering barrier function. This stimulatory effect could be blocked by basolateral atropine but not indomethacin. The cysteine and methionine oxidizing compounds, phenylarsine oxide and chloramine T respectively, mimicked the effect of H2O(2), except for a drop in transcolonic resistance after 30 min. In contrast to the observed stimulatory effect on basal secretion, cAMP-stimulated electrogenic ion transport was blunted by luminal H2O(2). However, the Ca(2+)-activated response remained unchanged.
H2O(2) may be an important selective modulator of intestinal ion and water secretion in certain pathologic conditions such as inflammation or ischemia-reperfusion by multiple mechanisms.
采用电生理和药理学方法,研究管腔暴露于过氧化氢(H2O2)及两种相关的硫醇氧化剂对天然结肠基础及刺激状态下氯离子分泌的影响。
将未剥离的大鼠远端结肠段安装于尤斯灌流小室中。使用双电压/电流钳监测未剥离结肠段的电位差、计算得出的电阻及短路电流。通过测量荧光探针(异硫氰酸荧光素,FITC)的黏膜至浆膜通量评估细胞旁通透性。
管腔暴露于过氧化氢可短暂刺激氯离子分泌,而不改变屏障功能。这种刺激作用可被基底外侧阿托品阻断,但不能被吲哚美辛阻断。半胱氨酸和甲硫氨酸氧化化合物,即氧化苯砷和氯胺T,分别模拟了H2O2的作用,但30分钟后跨结肠电阻下降。与观察到的对基础分泌的刺激作用相反,管腔H2O2使环磷酸腺苷(cAMP)刺激的电生性离子转运减弱。然而,钙激活反应保持不变。
在某些病理状态如炎症或缺血再灌注时,H2O2可能通过多种机制成为肠道离子和水分泌的重要选择性调节剂。