Effects of halogenated inhalated anesthetics on nitric oxide (NO) signal transduction system.

一氧化氮（NO）是由许多组织和细胞产生的独特分子。在中枢神经系统中，NO作为一种神经递质，介导兴奋性氨基酸刺激。提示一氧化氮的这些作用与记忆、意识和疼痛的表达有关。NO的受体是酶细胞鸟苷酸环化酶（GC），它是一种还原的含铁血红蛋白，催化cGMP的合成。NO通过与还原铁结合激活GC。卤代吸入挥发性麻醉药也已知通过还原铁与血红蛋白如细胞色素P-450和血红蛋白相互作用。虽然已经做了许多实验来确定吸入性麻醉药的作用部位，但它仍然是未知的。此外，多项研究表明，阻断兴奋性氨基酸- no - cgmp通路的多种药物具有麻醉作用。然后，我们检测了吸入挥发性麻醉剂对no刺激大鼠脑可溶性部分GC活性的影响。更多的脑溶性成分来自雄性Spague-Dawley大鼠。通过加入含NO溶液的脑溶部分和饱和挥发性麻醉缓冲液开始培养。分别用一氧化氮监测仪和气相色谱法监测一氧化氮和麻醉浓度。GC活性测定采用酶免疫法测定no信号转导途径的最终产物c-GMP。在低至2 × 10^<-9>的水平下，没有刺激的GC活动。主要的挥发性麻醉剂之一氟烷(H)剂量依赖性（0.5-2.7mM）抑制no刺激的GC活性。此外，H不刺激NO也能抑制脑可溶性部分GC活性。这些结果表明：1)H和NO竞争GC的活化位点（可能是还原铁）；2)除了与NO竞争外，H还有其他抑制GC活性的位点。需要进一步的研究来解释氟烷的这些作用是否与吸入的挥发性麻醉药的作用部位有关。少

Nitric Oxide (NO) is unique molecule produced by numerous tissues and cells. In CNS,NO acts as a neurotransmitter and mediates excitatory amino acid-stimulation. It is suggested that those action of NO is associated with expression of memory, consciousness and pain. The receptor for NO is enzyme celled guanylate cyclase (GC) which is a reduced iron-containing hemeprotein, catalyzing the synthesis of cGMP.NO activates GC by binding to the reduced iron. Halogenated inhalate volatile anesthetics is also known to interact with hemeprotein like cytochrome P-450 and hemoglobin through the reduced iron. Although many experiments were done to determine the site of action of inhalate volatile anesthetics, it is still unknown. In addtion, several studies indicate that various agents blocking the excitatory amino acid-NO-cGMP pathway have the anesthetic action. Then, we examine the effects of inhalate volatile anrsthetics on NO-stimulated GC activity in rat brain soluble fraction.The brain solubl … More e fraction was made from male Spague-Dawley rats. The incubation were initiated by adding brain soluble fraction with NO solution and satulated volatele anesthetics buffer. NO and anesthetic concentration were monitored with NO monitor and gasclomatoglaphy, respectively. GC activity was determined by measuring c-GMP,the final product of NO-signal trunsduction pathway, by enzymeimmunoassay. No stimulated GC activity at the lebel of as low as 2 X 10^<-9>. One of the main volatile anesthetics, halothane (H) dose-dependently (0.5-2.7mM) inhibited NO-stimulated GC activity. Moreover, GC activity was also inhibited by H without NO stimulation in brain soluble fraction. These results suggest that 1) : H and NO compete the site of activation of GC (probably reduced iron), 2) : bisides the competition with NO,H has other sites to inhibit GC activity.Further investigation should be needed to explain whether these effects of halothane is associated with the site of action of inhalated volatile anesthetics. Less