Benzodiazepines and GABA-GABAA receptor system in the cat carotid body.
Benzodiazepines and GABA-GABAA receptor system in the cat carotid body.
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DOI：
10.1007/978-90-481-2259-2_19
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发表时间：
2009
影响因子：
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通讯作者：
Ayuko Igarashi;N. Zadzilka;M. Shirahata
中科院分区：
文献类型：
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作者：
Ayuko Igarashi;N. Zadzilka;M. Shirahata
苯二氮卓类药物（BZ）可能通过增强呼吸控制系统中GABA A受体的活性来抑制通气，但确切的作用部位尚不清楚。本研究的目的是：（1）鉴定颈动脉体（CB）和岩神经节（PG）中的GABA A受体亚单位;（2）检测BZ是否通过CB化学感受单位中的GABA A受体发挥作用。组织取自安乐死的成年猫。从脑中提取RNA，测定几个GABA A受体亚基的cDNA序列。随后的RT-PCR分析证实CB和PG中α2、α3、β3和γ 2亚基的基因表达。CB中化学感受性球细胞（GC）和PG中神经元中检测到GABA和GABA A受体β3和γ2亚基的免疫反应性。两种BZ（咪达唑仑和地西泮）降低了CB对缺氧的神经反应。连续应用GABA A受体拮抗剂荷包牡丹碱可消除BZ的作用。总之，GABA-GABAA受体系统在CB化学感受系统中起作用。BZ通过增强GABA A受体活性抑制CB对缺氧的神经反应。
Benzodiazepines (BZs) suppress ventilation possibly by augmenting the GABAAreceptor activity in the respiratory control system, but precise sites of action are not well understood. The goals of this study were: (1) to identify GABAAreceptor subunits in the carotid body (CB) and petrosal ganglion (PG); (2) to test if BZs exert their effects through the GABAAreceptor in the CB chemosensory unit. Tissues were taken from euthanized adult cats. RNA was extracted from the brain, and cDNA sequences of several GABAAreceptor subunits were determined. Subsequent RT-PCR analysis demonstrated the gene expression of α2, α3, β3, and γ2 subunits in the CB and the PG. Immunoreactivity for GABA and for GABAAreceptor β3 and γ2 subunits was detected in chemosensory glomus cells (GCs) in the CB and neurons in the PG. The functional aspects of the GABA-GABAAreceptor system in the CB was studied by measuring CB neural output using in vitro perfusion setup. Two BZs, midazolam and diazepam, decreased the CB neural response to hypoxia. With continuous application of bicuculline, a GABAAreceptor antagonist, the effects of BZs were abolished. In conclusion, the GABA-GABAAreceptor system is functioning in the CB chemosensory system. BZs inhibit CB neural response to hypoxia by enhancing GABAAreceptor activity.