Triggiani M, Oriente A, Golino P, Gentile M, Battaglia C, Brevetti G, Marone G
Division of Clinical Immunology, University of Naples Federico II, Italy.
Biochem Pharmacol. 1999 Oct 15;58(8):1341-8. doi: 10.1016/s0006-2952(99)00204-x.
Propionyl-L-carnitine (PrC) has been shown to exert beneficial effects in the treatment of myocardial and peripheral ischemia in man. These conditions are associated with the activation of circulating neutrophils and platelets. To determine whether PrC could affect the synthesis of lipid mediators known to influence neutrophil and platelet functions, we explored the effects of PrC on the synthesis of platelet-activating factor (PAF) and arachidonic acid (AA) metabolites. Preincubation (90 min) of human neutrophils with PrC (0.1-100 microM) inhibited the synthesis of PAF and of a PAF analog (1-alkyl-1'enyl-2-acetyl-sn-glycero-3-phosphoethanolamine: AEGPE) induced in vitro by the calcium ionophore A23187. In contrast, concentrations of PrC up to 100 microM did not influence the uptake of exogenous AA or the A23187-induced release of AA and eicosanoids from neutrophils in vitro. PrC (1 microM) also inhibited PAF synthesis from human platelets stimulated in vitro with thrombin, but had no effect on thrombin-induced aggregation. Oral administration of PrC (2 g/day for two weeks) to five normal volunteers resulted in a significant inhibition of PAF and AEGPE synthesis by neutrophils stimulated with A23187 ex vivo, with no effect on AA or eicosanoid release. These data indicate that PrC selectively inhibits in vitro and ex vivo PAF synthesis from human neutrophils and platelets without influencing AA metabolism or eicosanoid release. This effect of PrC might represent an additional mechanism by which this molecule can exert protective effects in tissue ischemia and in other inflammatory diseases associated with neutrophil and platelet activation.
已证明丙酰 - L - 肉碱（PrC）在治疗人类心肌和外周缺血方面具有有益作用。这些病症与循环中的中性粒细胞和血小板的激活有关。为了确定PrC是否会影响已知影响中性粒细胞和血小板功能的脂质介质的合成，我们研究了PrC对血小板活化因子（PAF）和花生四烯酸（AA）代谢产物合成的影响。用PrC（0.1 - 100 microM）预孵育人中性粒细胞90分钟，可抑制钙离子载体A23187体外诱导的PAF和PAF类似物（1 - 烷基 - 1'-烯基 - 2 - 乙酰基 - sn - 甘油 - 3 - 磷酸乙醇胺：AEGPE）的合成。相比之下，高达100 microM的PrC浓度在体外不影响外源性AA的摄取或A23187诱导的中性粒细胞中AA和类花生酸的释放。PrC（1 microM）也抑制了凝血酶体外刺激的人血小板中PAF的合成，但对凝血酶诱导的聚集没有影响。对五名正常志愿者口服PrC（2 g/天，持续两周）导致离体用A23187刺激的中性粒细胞对PAF和AEGPE合成的显著抑制，对AA或类花生酸释放没有影响。这些数据表明，PrC选择性地抑制人中性粒细胞和血小板体外和离体PAF的合成，而不影响AA代谢或类花生酸释放。PrC的这种作用可能代表了该分子在组织缺血和其他与中性粒细胞和血小板活化相关的炎症性疾病中发挥保护作用的另一种机制。
