Halothane inhibits bradykinin-stimulated prostacyclin production in endothelial cells.
Halothane inhibits bradykinin-stimulated prostacyclin production in endothelial cells.
复制标题
氟烷抑制内皮细胞中缓激肽刺激的前列环素产生。
DOI：
10.1097/00000542-199410000-00019
复制
发表时间：
1994
期刊：
影响因子：
8.8
通讯作者：
Longnecker,DE
中科院分区：
文献类型：
--
作者：
Loeb,AL;O'Brien,DK;Longnecker,DE
氟烷和异氟醚改变多种细胞类型的信号转导和功能。血管对这些麻醉剂的反应可能归因于对血管活性介质产生的药物特异性作用。本研究探讨了氟烷和异氟烷对内皮细胞基础和激动剂刺激的前列环素产生的影响。方法通过6-酮-前列腺素F1 α（前列环素的稳定分解产物）的放射免疫测定来监测培养的牛主动脉内皮细胞的前列环素产生。结果氟烷和异氟烷（0.3-1 mM）都不会改变前列环素的产生。缓激肽（1 μ M）、三磷酸腺苷（ATP）（10 μ M）和蜂毒肽（1微克）。ml-1）刺激前列环素的产生。异氟烷对缓激肽、ATP或蜂毒肽的反应没有影响。氟烷抑制缓激肽的反应，但不ATP或蜂毒肽的反应。用百日咳毒素（100 ng. ml-1）抑制三磷酸鸟苷结合蛋白G α i的功能，但在氟烷存在或不存在的情况下均不改变对缓激肽的反应。预处理佛波酯12-肉豆蔻酸酯13-乙酸酯（100 nM），刺激蛋白激酶C的活性，并没有改变缓激肽刺激的前列环素的生产，并防止抑制缓激肽的反应halothane.ConclusionsIsoflurane刺激前列环素生产的增加没有影响。氟烷抑制缓激肽刺激的前列环素的产生，但不受ATP或蜂毒肽刺激。这些结果表明，氟烷介导的缓激肽刺激的前列环素产生的抑制不涉及百日咳毒素敏感的G蛋白，可能是由于氟烷在信号转导途径中的一些其他步骤的相互作用，包括蛋白激酶C的抑制。
BackgroundHalothane and isoflurane alter signal transduction and function in several cell types. Vascular responses to these anesthetics may be attributable to agent-specific effects on vasoactive mediator production. This study investigated the effects of halothane and isoflurane on basal and agonist-stimulated prostacyclin production by endothelial cells.MethodsProstacyclin production by cultured bovine aortic endothelial cells was monitored by radioimmunoassay of 6-keto-prostaglandin F1 alpha, the stable breakdown product of prostacyclin.ResultsNeither halothane nor isoflurane (0.3-1 mM), altered prostacyclin production. Bradykinin (1 microM), adenosine triphosphate (ATP)(10 microM), and melittin (1 microgram. ml-1) stimulated prostacyclin production. Isoflurane had no effect on responses to bradykinin, ATP, or melittin. Halothane inhibited the response to bradykinin but not the response to ATP or melittin. Pretreatment with pertussis toxin (100 ng. ml-1), to inhibit the function of the guanosine triphosphate-binding protein G alpha i, did not alter the response to bradykinin in the presence or absence of halothane. Pretreatment with phorbol 12-myristate 13-acetate (100 nM), to stimulate protein kinase C activity, did not alter bradykinin-stimulated prostacyclin production and prevented the inhibition of the response to bradykinin by halothane.ConclusionsIsoflurane had no effect on the increase in prostacyclin production stimulated by bradykinin. Halothane inhibited the bradykinin-stimulated prostacyclin production but not that stimulated by ATP or melittin. These results suggest that the halothane-mediated inhibition of bradykinin-stimulated prostacyclin production does not involve a pertussis toxin-sensitive G-protein and may result from an interaction of halothane at some other step in the signal transduction pathway, including the inhibition of protein kinase C.