Pharmacological characterisation of human 5-HT2 receptor subtypes

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.