Gonzalez E T, Gimeno A L, Gimeno M A
Centro de Estudios Farmacológicos y de Principios Naturales (CEFAPRIN), Consejo Nacional de Investigaciones Cientificas y Técnicas (CONICET), Buenos Aires, Argentina.
Prostaglandins Leukot Essent Fatty Acids. 1989 May;36(2):113-7. doi: 10.1016/0952-3278(89)90028-8.
The effects of leukotriene C4 (LTC4), nordihydroguaiaretic acid (NDGA) and FPL-55712, on the metabolism of labelled glucose (U14C-glucose) in uteri isolated from spayed rats and from spayed-estrogenized rats, incubated in the presence and in the absence of indomethacin, were explored. Indomethacin (10(-6)M), enhanced significantly 14CO2 formation from labelled glucose, both in uteri from ovariectomized rats and in uteri from ovariectomized-estrogenized animals. In uteri from spayed not-estrogenized rats, expose 'in vitro' to indomethacin, NDGA (10(-5)M), an inhibitor of the 5-lipoxygenase, as well as FPL-55712 (10(-5)M), a LT antagonist, reduced significantly the enhanced metabolism of glucose evoked by indomethacin, an inhibitor of the cyclo- oxygenase. On the other hand, LTC4 (10(-7)M), augmented the metabolism of labelled glucose, reaching values even greater than those induced by indomethacin. In the spayed-estrogenized group LTC4 (10(-10)-10(-7)M) enhanced the formation of labelled CO2 from labelled glucose as much as indomethacin (10(-6)M) did, whereas neither NDGA nor FPL-55712 were effective. In addition, in uteri from ovariectomized-estrogenized rats, incubated with indomethacin, NDGA and FPL-55712, decreased the augmenting action of indomethacin on glucose metabolism, whereas LTC4 (10(-10)-10(-7)M) evoked a complete reversal of the inhibitory influence of NDGA on the formation of 14CO2. The force-going results suggest that tissue 5-lipoxygenase products, particularly LTC4, are involved in the metabolism of labelled glucose by rat uteri, mainly when the cyclo-oxygenase pathway is inhibited by indomethacin and the tissue is deprived of estradiol.(ABSTRACT TRUNCATED AT 250 WORDS)
研究了白三烯C4(LTC4)、去甲二氢愈创木酸(NDGA)和FPL-55712对从切除卵巢的大鼠及切除卵巢并经雌激素处理的大鼠分离出的子宫中标记葡萄糖(U14C-葡萄糖)代谢的影响,实验分别在有和没有吲哚美辛存在的情况下进行。吲哚美辛(10(-6)M)显著增强了标记葡萄糖生成14CO2的过程,无论是在去卵巢大鼠的子宫还是在去卵巢并经雌激素处理动物的子宫中。在未用雌激素处理的去卵巢大鼠子宫中,“体外”暴露于吲哚美辛时,5-脂氧合酶抑制剂NDGA(10(-5)M)以及白三烯拮抗剂FPL-55712(10(-5)M)显著降低了由环氧化酶抑制剂吲哚美辛引起的葡萄糖代谢增强。另一方面,LTC4(10(-7)M)增强了标记葡萄糖的代谢,达到的值甚至高于吲哚美辛诱导的值。在切除卵巢并经雌激素处理的组中,LTC4(10(-10)-10(-7)M)与吲哚美辛(10(-6)M)一样,增强了标记葡萄糖生成标记CO2的过程,而NDGA和FPL-55712均无效。此外,在去卵巢并经雌激素处理的大鼠子宫中,与吲哚美辛、NDGA和FPL-55712一起孵育时,它们降低了吲哚美辛对葡萄糖代谢的增强作用,而LTC4(10(-10)-10(-7)M)引起NDGA对14CO2形成的抑制作用完全逆转。上述结果表明,组织5-脂氧合酶产物,特别是LTC4,参与大鼠子宫中标记葡萄糖的代谢,主要是在环氧化酶途径被吲哚美辛抑制且组织缺乏雌二醇时。(摘要截选至250字)