In vitro biosynthesis of cyclooxygenase metabolites in ovalbumin-sensitized and control lungs of guinea pigs.
In vitro biosynthesis of cyclooxygenase metabolites in ovalbumin-sensitized and control lungs of guinea pigs.
复制标题
豚鼠卵清蛋白致敏肺和对照肺中环氧合酶代谢物的体外生物合成。
DOI：
10.1016/0006-2952(82)90533-0
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发表时间：
1982
影响因子：
5.8
通讯作者：
Hitchcock,M
中科院分区：
文献类型：
--
作者：
Rothberg,KG;Hitchcock,M
Cyclooxygenase metabolism may regulate mediator release in anaphylaxis. Thein vitrobiosynthesis of cyclooxygenase metabolites was examined, using isolated microsomal membranes from ovalbumin-sensitized and control guinea pig lungs, under conditions in which the substrate concentration ([3H]arachidonic acid) was varied (5–168 μM). With microsomes from sensitized lungs, there was stimulation of cyclooxygenase activity at substrate concentrations from 20 to 100 μM, with the major increases in activity occurring in the biosynthesis of thromboxane B2and prostaglandin D2. At substrate concentrations greater than 100 μM, the biosynthesis of thromboxane B2and prostaglandin D2decreased in microsomes of sensitized lungs to the level of production found in control-lung microsomes. In contrast, prostacyclin production was significantly higher in the control-lung microsomes at the higher substrate concentrations. The ratio of prostacyclin to thromboxane production was lower in sensitized-lung microsomes at all substrate concentrations. No changes in the biosynthesis of prostaglandins F2αor E2were detected between the two groups. Kinetic analysis of the data demonstrated that the cyclooxygenases in control and sensitized-lung microsomes exhibited different apparentKmandVmaxvalues. When the enzymes from both the control and the sensitized-lung microsomes were assayed in the presence of indomethacin (1–10 μM), a cyclooxygenase inhibitor, thromboxane synthesis was preferentially inhibited. The microsomal enzymes from control and sensitized lungs showed similar responses to the drug. At the indomethacin concentrations used, no significant inhibition of prostacyclin or prostaglandin production occurred. The results of thesein vitroexperiments support the hypothesis that net changes in the biosynthesis of cyclooxygenase metabolites may modulate the anaphylactic response of the lungs in sensitized animals.
