Loeb A L, O'Brien D K, Longnecker D E
Department of Anesthesia, University of Pennsylvania, Philadelphia 19104-4283.
Anesthesiology. 1994 Oct;81(4):931-8. doi: 10.1097/00000542-199410000-00019.
Halothane 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.
Prostacyclin production by cultured bovine aortic endothelial cells was monitored by radioimmunoassay of 6-keto-prostaglandin F1 alpha, the stable breakdown product of prostacyclin.
Neither 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.
Isoflurane 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.
氟烷和异氟烷可改变多种细胞类型的信号转导及功能。血管对这些麻醉剂的反应可能归因于其对血管活性介质生成的特异性作用。本研究调查了氟烷和异氟烷对内皮细胞基础状态及激动剂刺激下前列环素生成的影响。
通过对前列环素的稳定分解产物6-酮-前列腺素F1α进行放射免疫测定，监测培养的牛主动脉内皮细胞中前列环素的生成。
氟烷和异氟烷（0.3 - 1 mM）均未改变前列环素的生成。缓激肽（1 μM）、三磷酸腺苷（ATP）（10 μM）和蜂毒肽（1 μg/ml）可刺激前列环素生成。异氟烷对缓激肽、ATP或蜂毒肽的反应无影响。氟烷抑制对缓激肽的反应，但不抑制对ATP或蜂毒肽的反应。用百日咳毒素（100 ng/ml）预处理以抑制鸟苷三磷酸结合蛋白Gαi的功能，在有或无氟烷存在的情况下，均未改变对缓激肽的反应。用佛波醇12-肉豆蔻酸酯13-乙酸酯（100 nM）预处理以刺激蛋白激酶C活性，未改变缓激肽刺激的前列环素生成，并防止了氟烷对缓激肽反应的抑制。
异氟烷对缓激肽刺激的前列环素生成增加无影响。氟烷抑制缓激肽刺激的前列环素生成，但不抑制ATP或蜂毒肽刺激的生成。这些结果表明，氟烷介导的对缓激肽刺激的前列环素生成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的其他步骤发生相互作用，包括对蛋白激酶C的抑制。
