LEUKOTRIENES IN BRAIN - NATURAL OCCURRENCE AND INDUCED CHANGES
LEUKOTRIENES IN BRAIN - NATURAL OCCURRENCE AND INDUCED CHANGES
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DOI：
10.1016/0006-8993(91)90222-h
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发表时间：
1991-07-05
期刊：
影响因子：
2.9
通讯作者：
COCEANI, F
中科院分区：
文献类型：
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作者：
HYNES, N;BISHAI, I;COCEANI, F
肽白三烯（SP-LTs）（总产品和单个LTC4和LTE4）和LTB4通过放射免疫测定法测定从清醒猫的第三脑室收集的脑脊液（CSF）。用γ-谷氨酰转肽酶粗品处理样品后，总SP-LT表示为LTE4。部分实验还测定了前列腺素（PG）E_2和血栓素（TXA_2）的稳定代谢产物血栓素（TX）B_2。在基础条件下，SP-LT和LTC始终是可测量的（分别为327 +/-14和244 +/-41 pg/ml），而在大多数情况下，天然LTE4低于测定阈值（60 - 280 pg/ml）。LTB4几乎检测不到（30 +/-2 pg/ml）或根本检测不到。PGE的含量通常低于TXB2（31 +/-4 vs 281 +/-47 pg/ml）。脑室内（i.c.v.）给予花生四烯酸（40 μ g）导致SP-LT水平增加4倍，与PGE 2（76倍）和TXB 2（23倍）相比，SP-LT水平相对较小且短暂，而天然LTE 4或LTB 4均无变化。血小板活化因子（PAF，1 μ g i.c.v.）也有类似的反应，尽管SP-LT升高（4倍）更持久。当PAF给药前注射吲哚美辛（500 μ g i.c.v.）时，SP-LT进一步升高（9倍），而PAF拮抗剂BN 52021（1 μ g i.c.v.）或5-脂氧合酶抑制剂U-60，257（75 μ g i.c.v.）和L-651，392（10 mg/kg p.o.）。PAF也有效地导致LTC4升高3倍。与PAF不同，热原（内毒素i.c.v.或i.v.;白细胞介素-1 i.v.）在不存在和存在吲哚美辛预处理的情况下，高于发热阈值的剂量对CSF中的LT水平没有影响。我们得出结论，SP-LT是CSF的正常成分，LTC4是主要种类。对PAF的反应符合化合物在炎症过程中的致病作用和对损伤的反应性变化。没有证据表明SP-LT参与发热的中枢机制。
Peptidoleukotrienes (SP-LTs) (both total product and individual LTC4 and LTE4) and LTB4 were measured by radioimmunoassay in cerebrospinal fluid (CSF) collected from the third ventricle of conscious cats. Total SP-LT was expressed as LTE4 after treating samples with crude gamma-glutamyltranspeptidase. Prostaglandin (PG) E2 and thromboxane (TX) B2, the stable metabolite of TXA2, were also assayed in part of the experiments. Under basal conditions, SP-LT and LTC, were consistently measurable (respectively, 327 +/- 14 and 244 +/- 41 pg/ml), while native LTE4 was below the threshold of the assay (60-280 pg/ml) in most cases. LTB4 was barely detectable (30 +/- 2 pg/ml) or not detectable at all. PGE, was normally less abundant than TXB2 (31 +/- 4 vs 281 +/- 47 pg/ml). Intracerebroventricular (i.c.v.) administration of arachidonic acid (40-mu-g) caused a 4-fold increase in SP-LT levels which was relatively small and transient compared to PGE2 (76-fold) and TXB2 (23-fold), while there was no change in either native LTE4 or LTB4. A similar response was obtained with platelet-activating factor (PAF, 1-mu-g i.c.v.), though SP-LT elevation (4-fold) was more persistent. A further rise in SP-LT (9-fold) was noted when PAF administration was preceded by indomethacin (500-mu-g i.c.v.), whereas PAF effect was reversed by pretreatment with either the PAF antagonist, BN52021 (l-mu-g i.c.v.), or the 5-lipoxygenase inhibitors, U-60,257 (75-mu-g i.c.v.) and L-651,392 (10 mg/kg p.o.). PAF was also effective in causing a 3-fold rise in LTC4. Unlike PAF, pyrogens (endotoxin i.c.v. or i.v.; interleukin-1 i.v.) at doses above threshold for fever had no effect on LT levels in CSF, both in the absence and presence of indomethacin pretreatment. We conclude that SP-LTs are a normal constituent of CSF, LTC4 being the major species. The response to PAF accords with a pathogenetic role of the compounds in inflammatory processes and the reactive changes to injury. No evidence was obtained for the involvement of SP-LTs in the central mechanism of fever.