Functional α2C-adrenoceptors in human neuroblastoma SH-SY5Y cells
Functional α2C-adrenoceptors in human neuroblastoma SH-SY5Y cells
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DOI：
10.1016/s0014-2999(99)00190-9
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发表时间：
1999-05-07
影响因子：
5
通讯作者：
Schoeffter, P
中科院分区：
文献类型：
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作者：
Parsley, S;Gazi, L;Schoeffter, P
进一步表征了人神经母细胞瘤 SH-SY5Y 细胞中 α(2)-肾上腺素受体介导的毛喉素刺激的环 AMP 积累抑制作用。 α(2)-肾上腺素受体激动剂 UK 14,304（5-溴-6-(2-咪唑啉-2-基氨基)喹喔啉）、羟甲唑啉、胍法辛、(-)-去甲肾上腺素和可乐定浓度依赖性地降低了该细胞系中环 AMP 的积累（E-max 约 50% 抑制）。激动剂 pEC(50) 值范围在 6.7 至 7.8 之间。可乐定是部分激动剂。 UK 14,304 的作用在百日咳毒素治疗后被阻断。 UK 14,304 的浓度-反应曲线通过以下拮抗剂（平均 pK(B) 值）平行向右移动：育亨宾 (8.17)、咪唑克生 (7.63)、哌唑嗪 (6.66)、 2-[2-(4-(2-甲氧基苯基)哌嗪-1-基)乙基]4,4-二甲基-1,3-(2H,4H)异喹啉二酮(ARC 239; 7.12)和2-(2,6-二甲氧基苯氧基乙基)氨基甲基1,4-苯并二恶烷(WB-4101; 8.12)。哌唑嗪和 ARC 239 相对较高的 pK(B) 值表明非 α(2A)-肾上腺素受体介导的作用。 WB-4101 相对较高的 pK(B) 值进一步表明 SH-SY5Y 细胞中的 α(2)-肾上腺素受体属于 α(2C) 亚型。通过逆转录酶-聚合酶链式反应 (RT-PCR) 对 α(2)-肾上腺素受体亚型表达的分析表明，SH-SY5Y 细胞中只存在 α(2C)-肾上腺素受体 mRNA。我们建议将SH-SY5Y细胞中毛喉素刺激的cAMP积累的抑制用作人类天然α(2C)-肾上腺素受体的功能模型。 (C) 1999 Elsevier Science B.V. 保留所有权利。
The alpha(2)-adrenoceptor mediating inhibition of forskolin stimulated cyclic AMP accumulation in human neuroblastoma SH-SY5Y cells was further characterized. The alpha(2)-adrenoceptor agonists, UK 14,304 (5-bromo-6-(2-imidazolin-2-ylamino)quinoxaline), oxymetazoline, guanfacine, (-)-noradrenaline and clonidine concentration-dependently decreased cyclic AMP accumulation in this cell line (E-max ca. 50% inhibition). Agonist pEC(50) values ranged between 6.7 and 7.8. Clonidine was a partial agonist. The effects of UK 14,304 were blocked after a pertussis toxin treatment. The concentration-response curves of UK 14,304 were shifted to the right in a parallel manner by the following antagonists (mean pK(B) values): yohimbine (8.17), idazoxan (7.63), prazosin (6.66), 2-[2-(4-(2-methoxyphenyl)piperazin-1-yl)ethyl]4,4-dimethyl-1,3-(2H,4H) isoquinolindione (ARC 239; 7.12) and 2-(2,6-dimethoxyphenoxyethyl)aminomethyl 1,4-benzodioxane (WB-4101; 8.12). The relatively high pK(B) values of prazosin and ARC 239 point to a non-alpha(2A)-adrenoceptor-mediated effect. The relatively high pK(B) value of WB-4101 further characterizes the alpha(2)-adrenoceptor in SH-SY5Y cells as being of the alpha(2C) subtype. The analysis of the expression of alpha(2)-adrenoceptor subtypes by reverse transcriptase-polymerase chain reaction (RT-PCR) revealed the exclusive presence of alpha(2C)-adrenoceptor mRNA in SH-SY5Y cells. We propose that inhibition of forskolin-stimulated cAMP accumulation in SH-SY5Y cells be used as a functional model of human, native alpha(2C)-adrenoceptors. (C) 1999 Elsevier Science B.V. All rights reserved.