Cockroach GABAB receptor subtypes: Molecular characterization, pharmacological properties and tissue distribution
Cockroach GABAB receptor subtypes: Molecular characterization, pharmacological properties and tissue distribution
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DOI：
10.1016/j.neuropharm.2014.08.022
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发表时间：
2015-01-01
影响因子：
4.7
通讯作者：
Blenau, W.
中科院分区：
文献类型：
--
作者：
Blankenburg, S.;Balfanz, S.;Blenau, W.
γ-氨基丁酸（GABA）是中枢神经系统（CNS）中主要的抑制性神经递质。其作用由亲离子型GABA（A）受体或亲代谢型GABA（B）受体介导。GABA（B）受体通过Gi/o调节G蛋白、离子通道和腺苷酸环化酶。在人类中，GABA（B）受体亚型参与神经和精神疾病的病因学。然而，在节肢动物中，G蛋白偶联受体家族的这些成员只是不充分的特点。有趣的是，生理数据揭示了GABA（B）受体在美洲大蠊（Periplaneta americana）中的重要功能。我们克隆了编码美洲大蠊GABA（B）受体亚型1和2（PeaGB 1和PeaGB 2）的cDNA。当这两种受体蛋白在哺乳动物细胞中共表达时，受体异聚体与GABA的激活导致cAMP产生的剂量依赖性降低。药理学特征不同于哺乳动物和果蝇GABA（B）受体。用多克隆抗体进行的蛋白质印迹分析揭示了PeaGB 1和PeaGB 2在美洲大蠊CNS中的表达。除了在脑中广泛分布外，PeaGB 1还在唾液腺和男性附属腺中表达。值得注意的是，在GABA能唾液神经元2中检测到PeaGB 1样免疫反应性，表明GABA（B）受体在该神经元中充当自受体。(C)2014爱思唯尔有限公司版权所有。
gamma-aminobutyric acid (GABA) is the predominant inhibitory neurotransmitter in the central nervous system (CNS). Its effects are mediated by either ionotropic GABA(A) receptors or metabotropic GABA(B) receptors. GABA(B) receptors regulate, via Gi/o, G-proteins, ion channels, and adenylyl cyclases. In humans, GABA(B) receptor subtypes are involved in the etiology of neurologic and psychiatric disorders. In arthropods, however, these members of the G-protein-coupled receptor family are only inadequately characterized. Interestingly, physiological data have revealed important functions of GABA(B) receptors in the American cockroach, Periplaneta americana. We have cloned cDNAs coding for putative GABA(B) receptor subtypes 1 and 2 of P. americana (PeaGB1 and PeaGB2). When both receptor proteins are co-expressed in mammalian cells, activation of the receptor heteromer with GABA leads to a dose-dependent decrease in cAMP production. The pharmacological profile differs from that of mammalian and Drosophila GABA(B) receptors. Western blot analyses with polyclonal antibodies have revealed the expression of PeaGB1 and PeaGB2 in the CNS of the American cockroach. In addition to the widespread distribution in the brain, PeaGB1 is expressed in salivary glands and male accessory glands. Notably, PeaGB1-like immunoreactivity has been detected in the GABAergic salivary neuron 2, suggesting that GABA(B) receptors act as autoreceptors in this neuron. (C) 2014 Elsevier Ltd. All rights reserved.