Hepatic Encephalopathy and Benzodiazepine Receptor Ligands-猫眼课题宝

肝性脑病和苯二氮卓受体配体

DOI：

10.1007/978-1-4612-4506-3_19

发表时间：

1989

期刊：

bioRxiv

影响因子：

通讯作者：

中科院分区：

文献类型：

作者：

E. Jones;S. H. Gammal;A. Basile;K. Mullen;M. Bassett;D. Schafer;P. Skolnick

苯二氮卓（BZ）受体配体与中枢神经系统（CNS）神经元上GABAA受体/氯离子通道复合物上的特异性结合位点相互作用（1）（图1）。如果超分子复合物本身参与肝性脑病（HE）综合征，则此类配体可能有助于或改善HE。该复合物包括BZ配体和GABA的不同受体，以及氯离子载体，其上有巴比妥酸盐和笼状惊厥剂（如印防己毒素）的结合位点。该复合物的效应子组分（氯离子通道）的激活由GABA与其受体的结合介导，并通过BZ激动剂或巴比妥酸盐与复合物上的离散位点的结合而增强。激活诱导复合物的构象变化，导致氯离子通道开放和神经元超极化（1）（图1）。这种GABA门控氯离子电导是GABA介导的抑制性神经传递或“GABA能紧张”的基础。

Benzodiazepine (BZ) receptor ligands interact with specific binding sites on the GABAA receptor/chloride channel complex on neurons in the central nervous system (CNS) (1) (Figure 1). Such ligands could contribute to or ameliorate hepatic encephalopathy (HE) if the supra-molecular complex itself is involved in this syndrome. The complex includes distinct receptors for BZ ligands and GABA, and a chloride ionophore on which there are binding sites for barbiturates and cage convulsants, such as Picrotoxin. Activation of the effector component of this complex, the chloride channel, is mediated by the binding of GABA to its receptor and is potentiated by the binding of a BZ agonist or a barbiturate to discrete loci on the complex. Activation induces conformational changes in the complex which result in opening of the chloride channel and hyperpolarization of the neuron (1) (Figure 1). This GABA-gated chloride ion conductance is the basis of GABA-mediated inhibitory neurotransmission or “GABAergic tone.”

Bicuculline enhances a negative component and diminishes a positive component of the visual evoked cortical potential in the cat.