Simmet T, Luck W, Delank W K, Peskar B A
Department of Pharmacology and Toxicology, Ruhr-University Bochum, F.R.G.
Brain Res. 1988 Jul 26;456(2):344-9. doi: 10.1016/0006-8993(88)90237-5.
Using sensitive radioimmunoassay techniques, the formation of cysteinyl-leukotrienes (LT) and prostaglandin (PG) F2 alpha was investigated in human brain tissue slices in vitro. Under basal conditions spontaneous release of considerable amounts of LTC4-like material and PGF2 alpha could be detected from slices of both human grey and white matter. Ionophore A23187 stimulated the release of large amounts of LTC4-like material while leaving unaffected the formation of the cyclo-oxygenase product PGF2 alpha. Incubation of grey or white matter in the presence of the cyclo-oxygenase inhibitor indomethacin inhibited the release of PGF2 alpha but did not affect that of LTC4-like material. Preincubation of brain tissue in the presence of the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) abolished the ionophore A23187-induced release of LTC4-like material from both grey and white matter and also significantly reduced the spontaneous release of LTC4-like material from white matter slices. Formation of PGF2 alpha was not affected by NDGA. Using the isolated guinea pig ileum the LTC4-like material was shown to possess biological activity which could be antagonized with the slow-reacting substance of anaphylaxis (SRS-A) antagonist FPL 55712. By reversed phase HPLC the immunoreactive LTC4-like material from human grey matter was shown to coelute with authentic LTC4, LTD4 and LTE4, while material from human white matter coeluted with authentic LTD4 and LTE4. The capacity of human brain tissue to synthesize cysteinyl-LT may be important for cellular functions in the central nervous system.
运用灵敏的放射免疫分析技术，在体外对人脑组织切片中半胱氨酰白三烯（LT）和前列腺素（PG）F2α的形成进行了研究。在基础条件下，可从人灰质和白质切片中检测到相当数量的LTC4样物质和PGF2α的自发释放。离子载体A23187刺激了大量LTC4样物质的释放，而对环氧化酶产物PGF2α的形成没有影响。在环氧化酶抑制剂吲哚美辛存在的情况下孵育灰质或白质，可抑制PGF2α的释放，但不影响LTC4样物质的释放。在脂氧合酶抑制剂去甲二氢愈创木酸（NDGA）存在的情况下对脑组织进行预孵育，消除了离子载体A23187诱导的灰质和白质中LTC4样物质的释放，并且也显著降低了白质切片中LTC4样物质的自发释放。PGF2α的形成不受NDGA影响。利用分离的豚鼠回肠，显示LTC4样物质具有生物活性，该活性可被过敏反应慢反应物质（SRS-A）拮抗剂FPL 55712拮抗。通过反相高效液相色谱法，显示来自人灰质的免疫反应性LTC4样物质与 authentic LTC4、LTD4和LTE4共洗脱，而来自人白质的物质与 authentic LTD4和LTE4共洗脱。人脑组织合成半胱氨酰-LT的能力可能对中枢神经系统的细胞功能很重要。
