頁籤選單縮合
題名 | Effects of Indomethacin on Intracellular pH and Na⁺/H⁺ Exchanger in the Human Monocytes= |
---|---|
作者 | Tsai, Yi-ting; Lee, Chung-yi; Chuang, Chao-chin; Lin, Hsueh-ju; Wu, Ching-hsia; Yang, Yu-zhe; Tsai, Chien-sung; Loh, Shih-hurng; |
期刊 | The Chinese Journal of Physiology |
出版日期 | 20150800 |
卷期 | 58:4 2015.08[民104.08] |
頁次 | 頁228-236 |
分類號 | 418.215 |
語文 | eng |
關鍵詞 | Fluorescent-BCECF; Human monocytes; Indomethacin; Intracellular pH; Microspectro-fluorimetry; Na⁺/H⁺ exchanger; NHE; |
英文摘要 | The ability to maintain optimal intracellular pH (pHi ) is an essential requirement for all cells. Na+ -H+ exchanger (NHE), a ubiquitously expressed transmembrane protein, has been found widely as a major acid extruder in many different cell types, including human monocytes. We therefore investigated the mechanism of the active pHi recovery from intracellular acidosis (induced by NH4Cl prepulse) using intracellular 2’,7’-bis (2-carboxethyl)-5(6)-carboxyl-fluorescein (BCECF) fluorescence in cultured human monocytes. Indomethacin is a potent, nonselective inhibitor of cyclooxygenases. Due to its toxicity, the clinical use of indomethacin as an analgesic-antipyretic agent is limited. However, it has recently been found that indomethacin can effectively treat many inflammatory/immune disorders. In this study, we further investigated the effect of indomethacin on the pHi and explored the underlying mechanism. In HEPES (nominally HCO3 - -free) Tyrode solution, a pHi recovery from induced intracellular acidosis could be blocked completely by 30 µM HOE 694, a specific NHE1 inhibitor, or by removing [Na+ ]o. Therefore, in the present study, we provided functional evidence, physiologically and pharmacologically, that the HCO3 - -independent acid extruder was mostly likely the NHE1 which was involved in acid extrusion in the human monocytes. Moreover, indomethacin (1 μM-1 mM) decreased pHi levels in a concentration-dependent manner and significantly suppressed the activity of the NHE1, suggesting that indomethacin-induced intracellular acidosis is caused both by the inhibition of NHE1 activity and the non-specified NHE1-independent acidifying mechanism. In conclusion, our present study demonstrates that NHE1 exists functionally in human monocytes, and the indomethacin-induced pHi decreasing is summation effects on NHE1-dependent and -independent mechanism. |
本系統之摘要資訊系依該期刊論文摘要之資訊為主。