Effects of Volatile Anesthetics on Phosphatidylinositol Turnover in Rat Cerebral Cortex.

大脑中的去甲肾上腺素途径被认为与麻醉作用的部位有关。中枢神经系统中的去甲肾上腺素(NE)通过α1肾上腺素能受体、G蛋白和磷脂酶C刺激磷脂酰肌醇(PI)的转运。在外周模型中，麻醉剂对PI的转运有抑制作用，提示G蛋白可能是麻醉药的作用靶点。本研究旨在阐明乙醇、巴比妥酸盐和挥发性麻醉剂对去甲肾上腺素(NE)刺激的大鼠大脑皮质棱柱PI代谢的影响。采用Brown等人的技术，检测与[~3H]肌醇孵育的大鼠大脑皮质棱柱中肌醇1.4.5-三磷酸(IP_3)的降解产物[~(3 H)]肌醇-1-磷酸([^~3H]IP_1)的积聚。我们观察了药物对去甲肾上腺素刺激的IP_1形成的影响。用柱层析法从肌醇中分离出[3 H]IP1，用液体闪烁计数器计数，以每分钟降解量(DPM)表示。用气相色谱法测定挥发性麻醉药的浓度。数据用均值&t；+-gt；sM表示，统计学意义用Fisher‘s保护最小显着性差异进行分析，p&lt；0.05为显著。乙醇和巴比妥酸盐对NE刺激的IP1形成有抑制作用，且呈剂量依赖性。氟烷和异氟烷不能抑制NE刺激的IP_1的形成。七氟醚以剂量依赖方式增强NE刺激的IP_1的形成。结果提示，这些对大脑皮层PI代谢的影响可能与其药理作用有关，但与麻醉作用无关。

Noradrenergic pathway in the brain have been thought to be ralated to the site of anesthetic action. Norepinephrine (NE) in the central nervous system stimulates phosphatidylinositol (PI) turnover through alpha_1 - adrenergic receptors, G-protein and phospholipase C.It was shown that anesthetics inhibited PI turnover in peripheral models, indicating that G protein was a possible target of anesthetics. This study was designed to clarify the effects of ethanol, barbiturates and volatile anesthetics on NE-stimulated PI turnover in rat cerebral cortical prisms.The technique of Brown et al.was used to detect [^3H] inositol-1-phosphate ([^3H] IP_1), a degradation product of inositol 1.4.5-trisphosphate (IP_3), accumulation in cerebral cortical prisms incubated with [^3H] myo-inositol. We examined the effects of drugs on the NE-stimulated IP_1 formation. The [^3H] IP_1 formed was separated from [^3H] myoinositol by column chromatography and counted with liquid scintillation counter and presented by degradation per minute (DPM). The concentration of volatile anesthetics was assayd with gaschromatography. Data were expressed as mean <plus-minus>SEM.Statistical significance was analyzed by Fisher's Protected Least Significant Difference with p<0.05 regarded as significant. The NE-stimulated IP1 formation was inhibited by ethanol and barbiturates in a dose dependent manner. The NE-stimulated IP_1 formation was not inhibited by halothane and isoflurane. Sevoflurane potentiated the NE-stimulated IP_1 formation in a dose dependent manner. The results suggest that these effects on the PI turnover in the cortex might be related to their pharmacological properties but not be involved in the anesthetic actions.