山莨菪碱对大鼠胸水中性白细胞花生四烯酸代谢的影响

本文研究了654-2对大鼠胸水中性白细胞代谢1-¹⁴C]AA及内源性AA的影响。大鼠白细胞AA经5-LPO代谢途径形成的主要产物为LTB₄及5-HETE,经CO途径的主要产物为HHT及TXB₂。654-2对白细胞代谢1-¹⁴C]AA无抑制作用,但显著减少白细胞从内源性AA形成的LTB₄,5-HETE,HHT及TXB₂。这种抑制作用与654-2呈剂量依赖关系。本实验结果表明,654-2抑制PG及LT的形成可能是影响了AA从胞膜的释放,而并非直接抑制CO及5-LPO。

EFFECTS OF ANISODAMINE ON THE METABOLISM OF ARACHIDONIC ACID BY RAT PLEURAL NEUTROPHILS

The effects of anisodamine (654-2) on the metabolism of arachidonic acid (AA) by rat pleural neutrophils were investigated. The major products of metabolism by 5-lipoxygenase (5-LPO), measured by HPLC, were LTB₄ and 5-HETE, whereas the major cyclooxygenase (CO) products measured by HPLC and RIA, were HHT and TXB₂. The formation of all products from endogenous AA by neutrophils was significantly depressed by 654-2 in a dose-dependent manner. At the concentration of 3 × 10^-4 mol/L the formation of LTB₄, 5-HETE, HHT and TXB₂ were decreased by 26, 29, 31 and 25%, respectively. This reduction was more than 40% when the concentration of 654-2 was 1 × 10^-3 mol/L. However, the inhibitory effect was not significant when the concentration of 654-2 was below 5 × 10^-5 mol/L. No effect of 654-2 on metabolism of 1-¹⁴C] AA by rat neutrophils was observed. The different effects of 654-2 on the metabolism of endogenous and exogenous AA indicate that the inhibitory effect of 654-2 on formation of both 5-LPO and CO products from endogenous substrate may be due to the reduction of AA release from cell membrane rather than inhibition of 5-LPO and CO activity.