Studies on the neural functions of platelet-activating factor

血小板活化因子（Platelet-activating factor，PAF）是一种磷脂介质，最初存在于炎症和免疫相关细胞中，具有多种生物学活性，具有重要的生理和病理意义。虽然PAF已在神经组织如脑中发现，但PAF在组织中的作用尚不清楚。我们研究了PAF的产生及其对肾上腺嗜铬细胞释放儿茶酚胺（CA）的影响。乙酰胆碱（ACh）可增加牛肾上腺嗜铬细胞PAF的表达。乙酰辅酶A乙酰转移酶活性在ACh刺激下迅速增加。PAF在高浓度时轻度增加CA的释放，并增强过量KCl诱导的CA释放和细胞内游离Ca^2+浓度（[Ca^2+]i）的升高。PAF对CA释放和[Ca^2+]i的作用可被河豚毒素阻断，可被钙拮抗剂部分阻断，但不被PAF拮抗剂BN 52021所抑制。低浓度（1-100 nM）PAF本身对CA释放没有影响，但增强ACh诱导的CA释放灌注肾上腺。PAF也能增强过量KCl诱导的CA释放，但在细胞外Ca^<2+>缺乏的情况下，PAF对咖啡因诱导的CA释放几乎没有影响。Lyso-PAF无作用。低浓度PAF对[Ca^<2+>]i无影响，但ACh-和过量KCl-可使[Ca^<2+>]i升高。BN 52021可拮抗PAF的作用。本实验结果为PAF可能在肾上腺嗜铬细胞CA释放中起调节作用提供了实验依据。

Platelet-activating factor (PAF), originally detected in inflammatory and immunerelated cells, is a phospholipid mediator exhibiting a variety of biological activities, and thus physiological and pathological importances. Although PAF has been found in the neuronal tissue such as the brain, the role of PAF in the tissue is not known. We examined the production of PAF and its effects on catecholamine (CA) release in adrenal chromaffin cells. Acetylcholine (ACh) increased the amount of PAF in bovine adrenal chromaffin cells. The activity of lyso-PAF: acetyl-CoA acetyltransferase rapidly increased in the cells stimulated with ACh. PAF slightly increased CA release at high concentrations, and enhanced excess KCl-induced release of CA and the rise of intracelular free Ca^<2+> concentration ([Ca^<2+>]i). The effects of PAF on CA release and [Ca^<2+>]i were blocked by tetrodotoxin and partly reduced by calcium antagonists, but not inhibited by PAF antagonist, BN 52021. Low concentrations (1-100 nM) of PAF by itself had no effect on CA release but potentiated ACh-induced CA release in perfused adrenal glands. PAF also potentiated excess KCl-induced CA release but had little effect on caffeine-induced release in the absence of extracellular Ca^<2+>. Lyso-PAF was without effect. Low concentrations of PAF had no effect on [Ca^<2+>]i but potentiated ACh- and excess KCl-induced the increase in [Ca^<2+>]i. The effect of PAF was antagonized by BN 52021. The present results provide the evidence that PAF may play a modulating role in the CA release from adrenal chromaffin cells.