Nemeth E F, Douglas W W
Eur J Pharmacol. 1980 Oct 31;67(4):439-50. doi: 10.1016/0014-2999(80)90185-5.
ETYA (5,8,11,14-eicosatetraynoic acid; 50-100 microM), which inhibits both cyclo-oxygenase and lipoxidase, inhibited histamine release evoked by secretagogues dependent on extracellular calcium (antigen, dextran, and concanavalin A) but failed to inhibit secretion elicited by secretagogues capable of mobilizing calcium from intracellular sites (48/80, polymyxin B, protamine sulfate and poly-L-lysine). Responses to these latter secretagogues were inhibited only by higher concentrations of ETYA (100-200 microM) that were cytotoxic. Secretion evoked by the calcium ionophore A23187 (0.1 microgram/ml) was inhibited at much lower concentrations of ETYA (1-10 microM) but this inhibition could not be overcome by increasing the concentration of calcium. Responses to higher concentrations of ionophore were not inhibited by ETYA except in amounts affecting cell viability. Like ETYA, each of several fatty acids, including arachidonic acid, were inhibitory towards histamine release evoked by A23187 or 48/80. The results indicate that EYTA acts at some early stage of stimulus-secretion coupling rather than on the final, common, calcium-activated steps of exocytosis. Moreover, this action may be unrelated to inhibition of lipoxidase or cyclooxygenase.
ETYA（5,8,11,14-二十碳四烯酸；50-100微摩尔）可抑制环氧化酶和脂氧化酶，它能抑制由依赖细胞外钙的促分泌剂（抗原、右旋糖酐和伴刀豆球蛋白A）诱发的组胺释放，但不能抑制由能够从细胞内位点动员钙的促分泌剂（48/80、多粘菌素B、硫酸鱼精蛋白和聚-L-赖氨酸）引发的分泌。对这些后一种促分泌剂的反应仅在具有细胞毒性的较高浓度ETYA（100-200微摩尔）时才受到抑制。钙离子载体A23187（0.1微克/毫升）诱发的分泌在低得多的ETYA浓度（1-10微摩尔）时即受到抑制，但这种抑制不能通过增加钙浓度来克服。对较高浓度离子载体的反应，除非ETYA的量影响细胞活力，否则不受其抑制。与ETYA一样，包括花生四烯酸在内的几种脂肪酸中的每一种，对由A23187或48/80诱发的组胺释放均有抑制作用。结果表明，EYTA作用于刺激-分泌偶联的某个早期阶段，而不是作用于胞吐作用最终的、共同的钙激活步骤。此外，这种作用可能与抑制脂氧化酶或环氧化酶无关。
