新型γ－氨基丁酸受体：GABAc受体

众多的证据表明，在神经系统，特别是视觉神经通路中，除通常的ＧＡＢＡＡ和ＧＡＢＡＢ受体之外，还存在着一种具有不同药理特性的ＧＡＢＡＣ受体。这种受体不为荷包牡丹碱（ｂｉｃｕｃｕｌｌｉｎｅ）所阻遏，亦不为氯苯氨丁酸（ｂａｃｌｏｆｅｎ）所激活，在激活后并不显示失敏现象，可能在视网膜中视杆通路的信，自传递和调控中起重要作用。

GABAc受体ρ1亚单位mRNA在大鼠视网膜和移植视网膜的定位

应用原位杂交组织化学技术及放射自显影技术 ,通过同位素 [35 S] -d ATP标记寡聚核苷酸探针 ,研究了 GABAc受体ρ1亚单位 m RNA在大鼠视网膜和移植视网膜的定位。实验结果发现 :ρ1亚单位 m RNA在大鼠视网膜和移植视网膜的分布相似 ,它们都分布在内核层中部和外侧部 (即近外网层侧 ) ,胞体呈椭圆形或卵圆形。正常大鼠视网膜 ρ1亚单位 m RNA杂交阳性细胞最先出现于生后第 12 d;移植视网膜出现于术后第 18d(即相当于正常视网膜生后第 10 d)。杂交阳性细胞的形态和位置提示 :表达 GABAc受体ρ1亚单位 m RNA的细胞可能是视网膜双极细胞。

蝇蕈醇激动GABA_C受体对青霉素致大鼠癫痫的影响

目的研究激动GABAC受体对青霉素诱导的大鼠癫痫发作、痫性放电的影响,探讨激动GABAC受体在内源性抗癫痫机制中的作用。方法青霉素致痫大鼠模型采用皮层定位注射青霉素(200 U)法制作。将144只成年健康SD大鼠随机分成四组:正常对照组,癫痫模型组,荷包牡丹碱(GABAA受体阻断剂)+高牛磺酸(GABAB受体阻断剂)处理组,和荷包牡丹碱+高牛磺酸+蝇蕈醇(GABAC受体激动剂)处理组。以癫痫发作持续时间和Racine痫性行为学分级作为效应指标;同步记录癫痫大鼠皮层脑电图(EcoG),分析痫样波持续时间、发放频率及最高振幅。结果大鼠运动皮层定位注射青霉素后,均出现Ⅰ-Ⅲ级发作,EcoG出现明显的棘波和棘慢波。癫痫发作高峰期给予荷包牡丹碱和高牛磺酸,可协同青霉素延长发作持续时间,增加发作级别,并增加痫样放电持续时间、频率和痫波振幅(P<0.05)。利用蝇蕈醇激动GABAC受体能明显降低大鼠癫痫发作持续时间、发作级别和痫样放电持续时间(P<0.05 vs荷包牡丹碱+高牛磺酸处理组),并且与癫痫模型组及荷包牡丹碱+高牛磺酸处理组比较,均能显著降低相同时间内的痫样波发放频率和振幅(P<0.05)。结论蝇蕈醇激动GABAC受体可加速终止青霉素与GABAA和GABAB受体阻断剂协同诱发大鼠癫痫发作,抑制痫性放电,提示GABAC受体的激活是内源性的抗癫痫机制之一。

Effects of 4-amino-2-methyl-cantharidinimide on GABA_C receptors

The antiepileptic effect of 4-amino-2-methyl-cantharidinimide（AMC） was reported,but its mechanism remains unknown.In this study,we investigated the effects of AMC on a rat model of penicillin-induced epilepsy.The doses of 88 and 22 mg/kg AMC and the dose of 154 mg/kg sodium valproate（VPA） were administered intragastrically（i.g.） 30 min before penicillin injection,respectively.The epileptiform activity was verified by electrocorticographic（ECoG） recordings.The levels of GABA and GABAC receptors in hippocampus were determined by immunohistochemistry,and real-time polymerase chain reaction（RT-PCR） technique was used to detect the mRNA expression of GABAC receptor ρ2.The mean frequency and amplification of spike epileptiform activity were significantly decreased in AMC and VPA-pretreated rats compared with those of non-pretreated penicillin-induced epilepsy（PIE） group.The levels of GABA,GABAC receptors and the mRNA expression of GABAC receptors ρ2 in AMC and VPA-pretreated rats were significantly increased as compared with PIE group.These findings indicate that AMC and VPA have an antiepileptic effect on PIE in rats,and the antiepileptic effect of AMC may be mediated by the GABAC receptors and GABA.

GABAC受体/通道的ρ1亚单位的研究进展

关于GABAC受体/通道的ρl亚单位,许多都是研究其在视网膜中的功能。近年来发现它在哺乳动物的CNS中也广泛存在,如脊髓、垂体、海马等。在视网膜中,由ρl亚单位组成的GABAC受体调节双极杆状细胞的视觉信号传输;而在脊髓中,ρl亚单位参与痛觉传输的调节。预测GABA受体/通道ρl亚单位在CNS中有更多重要的生理功能,特别是它的抑制调节作用。本文主要叙述ρl亚单位的特征和它在CNS中的分布与功能。

Differences in kinetics between GABA_C and GABA_A receptors on carp retinal bipolar cells

The present work was undertaken to characterize kinetics, including activation, desensitization and deactivation, of responses mediated by GABAA and GABAc receptors on carp retinal bipolar cells, using the whole-cell patch-clamp technique. It was revealed that the GABAC response was generally slower in kinetics than the GABAA response. Activation kinetics of both the receptors could be well fit by monoexponential functions with time constants r, being 44.57 ms (GABAC) and 10.86 ms (GABAA) respectively. Desensitization of the GABAA response was characterized by a fast and a slow exponential component with time constants of τfast = 2.16 s and τslow = 19.78 s respectively, whereas desensitization of the GABAc response was fit by a monoexponential function of the time constant T = 6.98 s. Deactivation at both the receptors was adequately described by biexponential functions with time constants being much higher for the GABAC response (τfast = 674.8 ms; τslow = 2 090 ms) than those for the GABAA response (τfast = 42.07 ms; τslow = 275.1 ms). These differences in kinetics suggest that GABAC and GABAA receptors may be involved in processing signals in different frequency domains.

Suppression of sustained and transient ON signals of amacrine cells by GABA is mediated by different receptor subtypes

Intracellular recordings were made from amacrine cells in the isolated, superfused carp retina, and the effects of γ-aminobutyric acid (GABA) on sustained and transient ON signals of these cells were studied. Exogenous GABA application partially suppressed the sustained response of ON amacrine cells, which could be completely reversed by picrotoxin (PTX), a chloride channel blocker, and by bicuculline (BCC), a specific GABA_A receptor antagonist. On the other hand, suppression by GABA of the ON response which was predominantly driven by rod signals in a certain portion of transient ON-OFF amacrine cells was completely blocked by PTX, but not by BCC, indicating that GABA_C receptors may be involved in the effect. These results suggest that GABA_A and GABA_C receptors may be respectively involved in mediating the transmission of sustained and transient signals in the carp inner retina.

胺甲氧斑蝥素对惊厥大鼠脑电和GABA_C受体ρ2 mRNA表达的影响

目的研究胺甲氧斑蝥素(AMOC)对电刺激大鼠坐骨神经和青霉素(PNC)协同诱发痫性放电模型的对抗作用及对皮层脑电图(EcoG)、诱发电位(CEP)和γ-氨基丁酸(GABA)C受体ρ2 mRNA表达的影响。方法建立电刺激坐骨神经和PNC协同诱发大鼠惊厥模型,丙戊酸钠(VPA)为阳性对照,以惊厥潜伏期和Racine痫性行为学分级作为评定药效指标,RM6240C型多道生物信号采集处理系统同步记录惊厥大鼠EcoG和CEP,观察AMOC的抗惊厥作用及对EcoG痫样波潜伏期、发放频率、最高振幅和CEP振幅的影响。采用实时荧光定量聚合酶链反应技术(RT-PCR)检测海马区GABAC受体ρ2 mRNA的表达变化。结果 AMOC和VPA均能明显延长大鼠惊厥潜伏期,减轻PNC诱发大鼠惊厥发作程度,明显延长痫性放电潜伏期,减少相同时间内痫样波发放频率,降低最高振幅和诱发电位振幅,与PNC模型组相比有显著性差异(P<0.01);PNC模型组GABAC受体ρ2 mRNA表达量较正常组下降,有统计学意义(P<0.05);AMOC和VPA组较PNC模型组明显升高,差别有统计学意义(P<0.01)。结论 AMOC和VPA均可对抗电刺激坐骨神经和PNC协同诱发大鼠惊厥发作,抑制痫性放电和诱发电位振幅,提高海马区GABAC受体ρ2 mRNA基因表达量。

脊髓及周围神经内GABA受体关于疼痛的研究进展

r-氨基丁酸(r-aminobutyric acid,GABA)是中枢神经系统重要的抑制性神经递质。GABA的功能由GABA受体(GABAreceptors,GABAR)所介导,GABA受体包括GABAA、GABAB、GABAC受体,GABAA受体、GABAC受体为离子型受体,GABAB受体为代谢性受体,属于G蛋白偶联受体C家族,并通过激活G蛋白系统来介导GABA引起的反应。在过去三十年里,有很多关于GABA受体在生物学和药理学方面处理疼痛的研究,现就GABA受体的结构、在脊髓及周围神经的分布、生理作用以及其与疼痛的关系等方面的研究进展进行综述。