POSSIBLE ROLE OF GANGLIOSIDES IN REGULATING AN ADENYLATE CYCLASE-LINKED 5-HYDROXYTRYPTAMINE (5-HT1) RECEPTOR
POSSIBLE ROLE OF GANGLIOSIDES IN REGULATING AN ADENYLATE CYCLASE-LINKED 5-HYDROXYTRYPTAMINE (5-HT1) RECEPTOR
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DOI：
10.1111/j.1471-4159.1985.tb10529.x
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发表时间：
1985-01-01
影响因子：
4.7
通讯作者：
DAWSON, G
中科院分区：
文献类型：
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作者：
BERRYKRAVIS, E;DAWSON, G
培养的NCB-20杂交细胞表达5-羟色胺(5-HT)的腺苷环化偶联受体，该受体在生物化学和药理学上与啮齿动物脑膜中的5-HT1受体相对应，除了与5-羟色胺的亲和力大大降低(大脑中160 NM与5 NM相比)。由于NCB-20细胞的神经节苷脂组成在定性和定量上也与啮齿类动物不同，因此我们检测了外源性神经节苷脂对5-HT1受体与5-羟色胺亲和力的影响。通过结合研究，GM1神经节苷脂(霍乱毒素受体)和四唾液酸神经节苷脂GQ1b对[~3H]5-羟色胺的受体亲和力都增加了10倍。在亚微摩尔浓度下，所有神经节苷脂均可显著降低5-Ht介导的细胞内环磷酸腺苷水平升高的EC50值。GQ1b能够最显著地增强5-羟色胺在调节环磷酸腺苷水平升高中的效力。神经节苷脂对DADLE或3，4-二羟基苯乙胺(DA)介导的环磷酸腺苷(CAMP)抑制作用无影响，提示5-羟色胺具有一定的特异性。我们的数据被解释为暗示多唾液酸神经节苷脂在调节5-HT1受体的亲和力和5-HT1受体-鸟嘌呤核苷酸结合蛋白腺苷环化酶复合体的偶联中发挥特殊作用。
Cultured NCB-20 hybrid cells express adenylate cyclate-coupled receptors for 5-hydroxytryptamine (5-HT) that correspond biochemically and pharmacologically to 5-HT1 receptors in rodent brain membrane preparations, apart from a much-reduced-affinity for 5-HT (160 nM compared to < 5 nM in brain). Since NCB-20 cells also differ from rodent brain both qualitatively and quantitatively in their ganglioside composition, the effects of exogenously added gangliosides on the affinity of the 5-HT1 receptor for 5-HT were tested. Both GM1 ganglioside (the cholera toxin receptor) and tetrasialoganglioside GQ1b produced a 10-fold increase in receptor affinity for [3H]5-HT, measured by binding studies. All gangliosides, at submicromolar concentrations, resulted in significantly reduced EC50 values for 5-Ht-mediated elevation of intracellular cyclic AMP levels. GQ1b had the capacity to most dramatically enhance the potency of 5-HT in mediating increases in cyclic AMP levels. Gangliosides had no effect on the potency of DADLE or 3,4-dihydroxyphenylethylamine (dopamine)-mediated depression of cyclic AMP levels, suggesting some specificity for 5-HT. Our data are interpreted as implying a specific role for polysialogangliosides in modulating the affinity of the 5-HT1 receptor and the coupling of the 5-HT1 receptor-guanine nucleotide binding protein adenylate cyclase complex.