Pharmacological characterisation of human 5-HT2 receptor subtypes
Pharmacological characterisation of human 5-HT2 receptor subtypes
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DOI：
10.1016/s0014-2999(01)00775-0
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发表时间：
2001-02-23
影响因子：
5
通讯作者：
Middlemiss, DN
中科院分区：
文献类型：
--
作者：
Jerman, JC;Brough, SJ;Middlemiss, DN
在相互矛盾的文献的推动下，本研究使用基于荧光成像板读取器 (FLIPR) 的 Ca2+ 测定比较了 SH-SY5Y 细胞中表达的人 5-羟色胺 (2) (5-HT2) 受体的药理学。 5-羟色胺 (5-HT) 增加 5-HT2A、5-HT2B 和 5-HT2C 受体的细胞内钙浓度 ([Ca2+](i))（分别为 pEC(50) = 7.73 +/- 0.03、8.86 +/- 0.04 和 7.99 +/- 0.04），并且这些反应被美舒麦角抑制（pK(B) = 7.42 +/- 0.06、8.77 +/- 0.10 和 9.52 +/- 0.11）。一系列选择性激动剂和拮抗剂在每种受体亚型上均显示出预期的药理学作用。丁酸钠预处理可增加 SH-SY5Y/5-HT2B（15 倍）和 SH-SY5Y/5-HT2C 细胞（7 倍）中的受体表达，并增加激动剂效力和相对功效。相反，丁酸钠预处理SH-SY5Y/5-HT2A细胞不影响受体表达。本研究提供了同质系统中 5-HT2 受体亚型的激动剂和拮抗剂药理学的直接比较，并证实激动剂的效力和功效随受体表达水平的变化而变化。 (C) 2001 Elsevier Science B.V. 保留所有权利。
Prompted by conflicting literature, this study compared the pharmacology of human 5-hydroxytryptamine(2) (5-HT2) receptors expressed in SH-SY5Y cells using a fluorometric imaging plate reader (FLIPR) based Ca2+ assay. 5-Hydroxytryptamine (5-HT) increased intracellular calcium concentration ([Ca2+](i)) at 5-HT2A, 5-HT2B and 5-HT2C receptors (pEC(50) = 7.73 +/- 0.03, 8.86 +/- 0.04 and 7.99 +/- 0.04, respectively) and these responses were inhibited by mesulergine (pK(B) = 7.42 +/- 0.06, 8.77 +/- 0.10 and 9.52 +/- 0.11). A range of selective agonists and antagonists displayed the expected pharmacology at each receptor subtype.Sodium butyrate pretreatment increased receptor expression in SH-SY5Y/5-HT2B (15-fold) and SH-SY5Y/5-HT2C cells (7-fold) and increased agonist potencies and relative efficacies. In contrast, sodium butyrate pretreatment of SH-SY5Y/5-HT2A cells did not affect receptor expression. The present study provides a direct comparison of agonist and antagonist pharmacology at 5-HT2 receptor subtypes in a homogenous system and confirms that agonist potency and efficacy varies with the level of receptor expression. (C) 2001 Elsevier Science B.V. All rights reserved.