Park Sun Young, Youm Ji Hyun, Jung Kyoung Chul, Sohn Uy Dong
Department of Pharmacology, College of Pharmacy, University of Chung-Ang, Seoul, 156-756, Korea.
Arch Pharm Res. 2008 Dec;31(12):1552-8. doi: 10.1007/s12272-001-2150-x. Epub 2008 Dec 20.
Under physiological conditions, hypochlorous acid (HOCl) is the major product of myeloperoxidase, a ferric heme enzyme released in inflammatory diseases. In the present study, we investigated the effect of HOCl compared to hydrogen peroxide (H2O2) on the vasoactive intestinal polypeptide (VIP)-induced relaxation of feline lower esophageal sphincter (LES) strips. Isometric tension on LES strips was measured using a force transducer. VIP induced the relaxation of basal LES tone in a concentration-dependent manner. Pretreatment with HOCl (10(-4) M) significantly reduced the VIP-induced relaxation at smaller concentrations than H2O2 (10(-3) M). VIP-induced relaxation is mediated via the Gi/o protein, since pretreatment with Pertussis Toxin (PTX) showed an inhibitory effect on the relaxation. HOCl showed an additional inhibitory effect on the reduced relaxation by PTX, indicating that HOCl might affect another G protein as well as Gi/o. However, HOCl did not affect SNP-, SIN-1-, and 8-br-cGMP-induced relaxation. Nor did HOCl modify the relaxation induced by either forskolin or db-cAMP in LES muscle strips. These results suggest that during short-term treatment, HOCl may damage the upstream events including G protein level, and result in alteration of LES tone in the feline esophagus, similar to the inhibitory effects of H2O2.
在生理条件下，次氯酸（HOCl）是髓过氧化物酶的主要产物，髓过氧化物酶是一种在炎症性疾病中释放的铁血红素酶。在本研究中，我们研究了与过氧化氢（H2O2）相比，HOCl对血管活性肠肽（VIP）诱导的猫食管下括约肌（LES）条带舒张的影响。使用力传感器测量LES条带的等长张力。VIP以浓度依赖性方式诱导基础LES张力的舒张。用HOCl（10^(-4) M）预处理在比H2O2（10^(-3) M）更低的浓度下显著降低了VIP诱导的舒张。VIP诱导的舒张是通过Gi/o蛋白介导的，因为用百日咳毒素（PTX）预处理对舒张有抑制作用。HOCl对PTX降低的舒张显示出额外的抑制作用，表明HOCl可能影响另一种G蛋白以及Gi/o。然而，HOCl不影响SNP、SIN-1和8-溴-cGMP诱导的舒张。HOCl也不改变LES肌条中福斯可林或二丁酰环磷腺苷（db-cAMP）诱导的舒张。这些结果表明，在短期治疗期间，HOCl可能损害包括G蛋白水平在内的上游事件，并导致猫食管中LES张力的改变，类似于H2O2的抑制作用。
