Jerman J C, Brough S J, Gager T, Wood M, Coldwell M C, Smart D, Middlemiss D N
Neuroscience Research, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Third Avenue, Essex CM19 5AW, Harlow, UK.
Eur J Pharmacol. 2001 Feb 23;414(1):23-30. doi: 10.1016/s0014-2999(01)00775-0.
Prompted by conflicting literature, this study compared the pharmacology of human 5-hydroxytryptamine2 (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 (pKB=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-HT(2A) cells did not affect receptor expression. The present study provides a direct comparison of agonist and antagonist pharmacology at 5-HT(2) receptor subtypes in a homogenous system and confirms that agonist potency and efficacy varies with the level of receptor expression.
受相互矛盾的文献启发，本研究使用基于荧光成像板读数器（FLIPR）的Ca2+检测方法，比较了在SH-SY5Y细胞中表达的人5-羟色胺2（5-HT2）受体的药理学特性。5-羟色胺（5-HT）在5-HT2A、5-HT2B和5-HT2C受体处增加细胞内钙浓度（[Ca2+]i）（pEC(50)分别为7.73±0.03、8.86±0.04和7.99±0.04），这些反应被美舒麦角抑制（pKB分别为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表现出预期的药理学特性。丁酸钠预处理增加了SH-SY5Y/5-HT2B细胞（15倍）和SH-SY5Y/5-HT2C细胞（7倍）中的受体表达，并增加了激动剂的效力和相对效能。相比之下，丁酸钠对SH-SY5Y/5-HT(2A)细胞的预处理不影响受体表达。本研究在同质系统中对5-HT(2)受体亚型的激动剂和拮抗剂药理学特性进行了直接比较，并证实激动剂的效力和效能随受体表达水平而变化。
