Enhancement by baclofen of the Gs-coupled receptor-mediated cAMP production in Xenopus oocytes expressing rat brain cortex poly (A)+ RNA: a role of G-protein beta gamma subunits.
Enhancement by baclofen of the Gs-coupled receptor-mediated cAMP production in Xenopus oocytes expressing rat brain cortex poly (A)+ RNA: a role of G-protein beta gamma subunits.
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巴氯芬增强表达大鼠脑皮质多聚 (A) RNA 的非洲爪蟾卵母细胞中 Gs 偶联受体介导的 cAMP 产生：G 蛋白 β γ 亚基的作用。
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发表时间：
1997
期刊：
影响因子：
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通讯作者：
F. Izumi
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作者：
Y. Uezono;Y. Ueda;S. Ueno;I. Shibuya;N. Yanagihara;Y. Toyohira;H. Yamashita;F. Izumi
我们研究了GABA-B受体在表达来自大鼠大脑皮层的poly (A)+ RNA的爪蟾卵母细胞中增强gs偶联受体介导的cAMP生成的机制。我们表达了囊性纤维化跨膜传导调节基因（CFTR）作为卵母细胞cAMP变化的报告基因。GABA-B激动剂（-）巴氯芬增强肾上腺素能β 2激动剂异丙肾上腺素或血管活性肠肽（VIP）诱导的CFTR电流，而（-）巴氯芬单独不引起任何电流。（-）巴氯芬增强电流被GABA-B拮抗剂2-OH氯氯芬抑制。（-）巴氯芬的增强作用通过共表达腺苷酸环化酶（AC） II型进一步增强，AC II型是一种被G β γ和G α s激活的同型，而AC III型对G β γ不敏感。此外，百日咳毒素（PTX）预处理卵母细胞消除了（-）巴氯芬的增强作用。这些结果表明，在GABA-B激活后，ptx敏感的G蛋白释放的G β γ激活了AC II型（或IV型），这一过程需要G α s被gs偶联受体激活。
We investigated the mechanism by which GABA-B receptors enhance the Gs-coupled receptor-mediated cAMP production in Xenopus oocytes expressing poly (A)+ RNA derived from rat brain cortex. We expressed the cystic fibrosis transmembrane conductance regulator gene (CFTR) as a reporter for cAMP changes in oocytes. The GABA-B agonist (-)baclofen enhanced the adrenergic beta 2 agonist isoproterenol- or vasoactive intestinal peptide (VIP)-induced CFTR currents, whereas (-)baclofen alone did not cause any currents. The (-)baclofen-enhanced currents were inhibited by the GABA-B antagonist 2-OH saclofen. The enhancement by (-)baclofen was further augmented by coexpressing adenylyl cyclase (AC) type II, an isotype activated by G beta gamma and G alpha s, but not by coexpressing AC type III, an isotype insensitive to G beta gamma. Moreover, pretreatment of the oocytes with pertussis toxin (PTX) abolished the enhanced effect of (-)baclofen. These results indicate that upon GABA-B activation, the G beta gamma released from PTX-sensitive G-proteins activates the AC type II (or IV), and this process requires the G alpha s activation by Gs-coupled receptors.