Inhalational anesthetics up-regulate constitutive and lipopolysaccharide-induced inducible nitric oxide synthase expression and activity
Inhalational anesthetics up-regulate constitutive and lipopolysaccharide-induced inducible nitric oxide synthase expression and activity
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DOI：
10.1124/mol.52.4.606
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发表时间：
1997-10-01
影响因子：
3.6
通讯作者：
Johns, RA
中科院分区：
文献类型：
--
作者：
Zuo, ZY;Johns, RA
一氧化氮 (NO) 是一种重要的生物信使，参与调节血管张力、神经传递、炎症反应和宿主防御。吸入麻醉药已被证明可以抑制多种组织中 NO 信号通路的功能。此外，NO信号通路的急性抑制显着降低了麻醉所需的氟烷或异氟烷的肺泡浓度，这表明NO信号通路在麻醉和意识机制中的作用。我们现在报道，吸入麻醉剂影响一氧化氮合酶 (NOS) (EC 1.14.13.39) 的基因表达，一氧化氮合酶是从 L-精氨酸合成 NO 的酶。在临床相关浓度下，氟烷和异氟烷均显着上调脂多糖处理的巨噬细胞（诱导型 NOS；II 型 NOS）和牛肺内皮细胞（内皮组成型 NOS；III 型 NOS）中 NOS 的 mRNA、蛋白质和活性水平。这是吸入麻醉药与 NO 信号通路之间的一种新型相互作用，对临床医学和实验生物学具有广泛的影响。
Nitric oxide (NO) is an important biological messenger involved in the regulation of blood vessel tone, neurotransmission, inflammatory responses, and host defenses. inhalational anesthetics have been shown to inhibit the function of the NO signaling pathway in a variety of tissues. In addition, acute inhibition of the NO signaling pathway significantly reduced the required alveolar concentration of halothane or isoflurane for anesthesia, which suggests a role for the NO signaling pathway in mechanisms of anesthesia and consciousness. We now report that inhalational anesthetics affect gene expression of nitric oxide synthases (NOS) (EC 1.14.13.39), the enzymes that synthesize NO from L-arginine. Both halothane and isoflurane, at clinically relevant concentrations, significantly up-regulate the mRNA, protein, and activity level of NOS in lipopolysaccharide-treated macrophages (inducible NOS; type II NOS), and bovine pulmonary endothelial cells (endothelial constitutive NOS; type III NOS). This is a novel interaction between inhalational anesthetics and the NO signaling pathway and has wide-ranging implications for both clinical medicine and experimental biology.