Inhibition of inducible nitric oxide synthase expression by adrenocorticotropin in endotoxin-treated murine macrophages

• Main Authors: Li-Jen Tsai, 蔡麗忍
• Other Authors: Chieh-Fu Chen
• Format: Others
• Language: zh-TW
• Published: 1999
• Online Access: http://ndltd.ncl.edu.tw/handle/85386198296635034161

碩士 === 國立陽明大學 === 藥理學研究所 === 87 === Nitric oxide (NO) plays an important role in blood pressure homeostasis and regional blood flow. Under physiological conditions, generation of NO from L-arginine by the constitutive NO synthase present in vascular endothelial cells (eNOS) keeps the vasculature in a permanent state of active vasodilation. In other conditions such as endotoxic and hemorrhagic shock, where abnormal NO production plays a key pathogenetic role. Adrenocorticotropin (ACTH) also can influence blood pressure. To characterize the effects of ACTH on NO production, we investigated the effects of varying concentrations of various fragments of ACTH on LPS induced NO production in a murine macrophage cell line RAW264.7. Treatments with ACTH or its fragments at various concentrations (10-11~10-5M) for the full course of 20 hours or 6-8 hours prior to the termination of the experiment all attenuated LPS induced NO production in RAW cells. Western blot studies indicated that ACTH1-24 could inhibit both the synthesis and activity of iNOS. Lyons et al postulated that leukocytes could serve as an extrapituitary source of ACTH produced in response to LPS. Our ACTH ELISA data also indicates that LPS lower ACTH concentraction in RAW264.7. In conclusion, when treated with LPS, there is an inducible NO production and decrease in ACTH in RAW264.7 while exogenous ACTH inhibits iNOS expression.