Interaction of anesthetic barbiturates with the phosphoinositide-dependent pathway of signal transduction.
Interaction of anesthetic barbiturates with the phosphoinositide-dependent pathway of signal transduction.
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麻醉巴比妥类药物与磷酸肌醇依赖性信号转导途径的相互作用。
DOI：
10.1111/j.1749-6632.1991.tb33870.x
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发表时间：
1991
影响因子：
5.2
通讯作者：
Brockerhoff,H
中科院分区：
文献类型：
--
作者：
Deshmukh,DS;Kuizon,S;Chauhan,VP;Brockerhoff,H
巴比妥类药物常用作麻醉药、催眠药和抗惊厥药，然而，它们的生物化学作用机制尚不清楚。巴比妥类药物被认为是通过作用于神经元膜，特别是突触膜而产生药理学作用。这些药物已被证明能增强γ-氨基丁酸（GABA）和地西泮与其受体的结合，并抑制GABA拮抗剂的结合。我们最近的研究表明，巴比妥类药物能有效地抑制突触体中磷脂酰肌醇4，5-二磷酸（PIP）的生物合成和蛋白激酶C（PKC）的活性。这表明受体偶联磷酸肌醇级联反应是巴比妥类药物作用的一个可能的生化靶点。脑中的两种毒蕈碱受体（M1和M2）都与磷酸肌醇系统偶联。这些受体的刺激引起磷脂酶C的活化，磷脂酶C将PIP水解为肌醇1，4，5-三磷酸（IP）和二酰基甘油（DG）。三磷酸肌醇从细胞内储存释放钙，而二酰甘油刺激PKC。6在大鼠突触体和突触神经体制备物的研究中，我们研究了不同巴比妥酸盐对磷酸肌醇代谢酶和卡巴胆碱介导的肌醇磷脂水解刺激的影响。
Thc barbiturates are commonly used as anesthetics, hypnotics, and anticonvulsant drugs; however, their biochemical mode of action is not yet clearly understood. Barbiturates are thought to cause their pharmacological effects by acting on neuronal membranes, particularly synaptic membranes. The drugs have been shown to enhance the binding of y-aminobutyric acid (GABA) and diazepam to their receptors and to inhibit the binding of GABA antagonists.', 2 Our recent studies showed that the barbiturates effectively inhibit the in vitro biosynthesis of phosphatidylinositol 4, 5-bisphosphate (PIP,) and the activity of protein kinase C (PKC) in synapto~ omes.~.~ This suggests that the receptor-coupled phosphoinositide cascade represents'a possible biochemical target for barbiturate action. Both muscarinic receptors (M1 and M2) in brain are coupled to the phosphoinositide system.'Stimulation of these receptors causes activation of phospholipase C, which hydrolyzes PIP, to inositol1, 4, 5-trisphosphate (IP,) and diacylglycerol (DG). Inositoltrisphosphate releases calcium from intracellular stores, whereas diacylglycerol stimulates PKC. 6 In this study of rat synaptosomes and synaptoneurosoma1 preparations we investigate the effects of different barbiturates on the enzymes of phosphoinositide metabolism and on the carbachol-mediated stimulation of the hydrolysis of inositol phospholipids.