INFLUENCE OF ETHANOL AND GLUCOCORTICOIDS ON GABA RECEPTORS IN THE CNS

乙醇和糖皮质激素对中枢神经系统 GABA 受体的影响

• 批准号: 4687730
• 负责人: R ESKAY
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/4687730
• 关键词: Cushing's syndrome; alcoholism /alcohol abuse; barbiturates; benzodiazepines; brain cell; ethanol; gamma aminobutyrate; glucocorticoids; neurochemistry; neuropharmacologic agent; synaptosomes

Ethanol exerts a dose-dependent stimulatory or inhibitory effect on the CNS; the mechanism of these effects is not, however, clear. Ethanol alters the action of several centrally acting GABA-ergic drugs, such as benzodiazepines and barbiturates, which suggests that ethanol interacts with GABA receptors. Ethanol exerts a biphasic effect on the binding of muscimol (GABA-A agonist) to GABA receptors in synaptosomal membranes obtained from different brain regions. Muscimol binding is inhibited at concentrations of ethanol ranging from 1.5 mM to 6 mM, whereas it is enhanced at higher concentrations. Decreased muscimol binding in the presence of low levels of ethanol was found to be due to reduced ligand affinity to the GABA receptors, whereas enhanced muscimol binding at high ethanol concentrations was due to increased receptor number. Glucocorticoids also appear to act directly on central GABA receptors, but in a dose-dependent manner opposite to that of ethanol. Nanomolar concentrations of glucocorticoids enhance muscimol binding, whereas micromolar concentrations inhibit binding. These effects are due to increased receptor affinity for the ligand and a decreased receptor number in the presence of low or high levels of glucocorticoids, respectively.

乙醇具有剂量依赖性的刺激或抑制作用。 中枢神经系统；然而，这些作用的机制尚不清楚。乙醇改变了 几种中枢作用的GABA能药物的作用 苯二氮卓类和巴比妥酸盐，这表明乙醇相互作用 通过GABA受体。乙醇对其结合具有双相效应。 麝香酚(GABA-A激动剂)对突触体膜上GABA受体的影响 取自不同的大脑区域。麝香酚结合在以下位置被抑制 乙醇浓度从1.5毫米到6毫米不等，而它是 在较高浓度下增强。降低了在体内的蝇硫醇结合 低水平乙醇的存在被发现是由于配体的减少。 与GABA受体的亲和力，而在较高的 乙醇浓度是由于受体数目增加所致。 糖皮质激素似乎也直接作用于中枢GABA受体，但 以与乙醇相反的剂量依赖方式。纳摩尔 糖皮质激素的浓度增加了蝇类激素的结合，而 微摩尔浓度抑制结合。这些影响是由于 受体对配体的亲和力增加而受体数量减少 分别在存在低水平或高水平糖皮质激素的情况下。