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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Effects of T-588, a novel cognitive enhancer, on ADP-ribosylation of G(s alpha) by cholera toxin and cyclic AMP accumulation in rat cerebral cortex.
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Effects of T-588, a novel cognitive enhancer, on ADP-ribosylation of G(s alpha) by cholera toxin and cyclic AMP accumulation in rat cerebral cortex.

机译:T-588,一种新型的认知增强剂,对霍乱毒素和大鼠大脑皮质中环AMP积累的G(s alpha)的ADP核糖基化的影响。

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We investigated the effects of R(-)-1-(benzo[b]thiophen-5-yl)-2-[2-(N,N-diethylamino)ethoxy]ethan ol hydrochloride (T-588), a novel cognitive enhancer, on trimeric GTP-binding proteins (G proteins) and cyclic AMP accumulation in rat cerebral cortex. T-588 (0.1-1.0 mM) inhibited the ADP-ribosylation of alpha subunit of Gs in a concentration-dependent manner. Auto-ADP-ribosylation of CTX was not inhibited by T-588. The stimulatory effect of guanosine 5'-(3-O-thio)triphosphate (GTPgammaS) on CTX-catalyzed ADP-ribosylation was attenuated by adding T-588 in assay mixture. ADP-ribosylation of Gi/Go by pertussis toxin was slightly inhibited by T-588. Isoproterenol-stimulated cyclic AMP accumulation was inhibited by adding 3 mM T-588 to rat cerebral cortical slices. Next, we investigated the effects of isoproterenol and T-588 on GTPgammaS binding. Membranes were first incubated with or without isoproterenol and T-588 in the presence of 0.2mM GTPgammaS, then cholate extract preparations were prepared from the washed membranes. Interestingly, the [32P]ADP-ribosylation of G(s alpha) was enhanced not only by isoproterenol but also by T-588. Although the obtained results are apparently inconsistent, T-588 seems to interact with G proteins, specifically Gs.
机译:我们调查了R(-)-1-(苯并[b]噻吩-5-基)-2- [2-(N,N-二乙氨基)乙氧基]乙乙醇盐(T-588)的作用,这是一种新的认知方法三聚体GTP结合蛋白(G蛋白)和大鼠大脑皮层中环AMP积累的增强子。 T-588(0.1-1.0 mM)以浓度依赖性方式抑制Gs的α亚基的ADP-核糖基化。 TTX 588不抑制CTX的自动ADP核糖基化。通过在分析混合物中添加T-588,减弱了鸟嘌呤5'-(3-O-硫代)三磷酸(GTPgammaS)对CTX催化的ADP-核糖基化的刺激作用。 T-588轻微抑制百日咳毒素对Gi / Go的ADP核糖基化。向大鼠大脑皮层切片中加入3 mM T-588可抑制异丙肾上腺素刺激的环AMP积累。接下来,我们研究了异丙肾上腺素和T-588对GTPgammaS结合的影响。首先在0.2mMGTPγS存在下,在有或没有异丙肾上腺素和T-588的情况下孵育膜,然后从洗涤过的膜制备胆酸盐提取物制剂。有趣的是,G(s alpha)的[32P] ADP-核糖基化不仅被异丙肾上腺素增强,还被T-588增强。尽管获得的结果显然不一致,但T-588似乎与G蛋白(特别是Gs)相互作用。

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