Skelly M M, O'Donoghue D P, Baird A W
Division of Gastroenterology, St. Vincent's Hospital, Dublin, Ireland.
Digestion. 2001;63(2):124-9. doi: 10.1159/000051880.
BACKGROUND/AIMS: Activation of cells within the lamina propria can cause electrogenic chloride secretion across intestinal epithelia by release and/or synthesis of mediator molecules, including reactive oxygen metabolites (ROMs). In this investigation we examined whether indirect (immune) stimulation of ion transport across rat colon was ROM-mediated.
Paired segments of rat colon, stripped of underlying smooth muscle, were mounted on Ussing chambers in order to measure electrogenic ion transport. Changes in short circuit current (SCC) were used as a measure of net electrogenic ion transport measured in response to the bacterial tri-peptide formyl-Met-Leu-Phe (fMLP) which was used to activate lamina propria neutrophils. The effect of the established anti-oxidants catalase and diethyldithiocarbamate (DDTC) and the putative anti-oxidant taurine upon immune-stimulated ion transport was examined.
The anti-oxidant DDTC but not catalase significantly attenuated ion transport responses to fMLP. Taurine applied basolaterally reduced ion transport response to fMLP but not to the directly acting secretagogues forskolin. Taurine applied apically enhanced ion transport responses to fMLP.
Anti-oxidants, including taurine, may be useful in treatment of colitis. The enhancement of effect seen when taurine was applied apically may have negative implications regarding the therapeutic usefulness of taurine administration to the lumenal compartment.
背景/目的:固有层内的细胞激活可通过释放和/或合成包括活性氧代谢产物(ROMs)在内的介质分子,引起肠道上皮细胞的电致氯化物分泌。在本研究中,我们检测了大鼠结肠离子转运的间接(免疫)刺激是否由ROM介导。
将去除下层平滑肌的大鼠结肠配对段安装在尤斯灌流小室上,以测量电致离子转运。短路电流(SCC)的变化用作净电致离子转运的指标,该指标是针对用于激活固有层中性粒细胞的细菌三肽甲酰甲硫氨酸-亮氨酸-苯丙氨酸(fMLP)进行测量的。检测了已确立的抗氧化剂过氧化氢酶和二乙基二硫代氨基甲酸盐(DDTC)以及假定的抗氧化剂牛磺酸对免疫刺激的离子转运的影响。
抗氧化剂DDTC而非过氧化氢酶显著减弱了对fMLP的离子转运反应。从基底外侧施加牛磺酸可降低对fMLP的离子转运反应,但对直接作用的促分泌剂福斯可林无此作用。从顶端施加牛磺酸可增强对fMLP的离子转运反应。
包括牛磺酸在内的抗氧化剂可能对结肠炎的治疗有用。顶端施加牛磺酸时所观察到的效果增强可能对向肠腔给予牛磺酸的治疗效用具有负面影响。