Subtle Differences among 5-HT3AC, 5-HT3AD, and 5-HT3AE Receptors Are Revealed by Partial Agonists

5-HT3 receptors are members of the Cys-loop family of ligand-gated ion channels, and, like most members of this family, there are multiple subunits that can contribute to functional pentameric receptors. 5-HT3A and 5-HT3AB receptors have been extensively characterized, but there are few studies on 5-HT3AC, 5-HT3AD, and 5-HT3AE receptors. Here we explore the properties of a range of partial agonists at 5-HT3AC, 5-HT3AD, and 5-HT3AE receptors following expression in Xenopus oocytes. The data show that the characteristics of receptor activation differ in the different heteromeric receptors when they are challenged with 5-HT, m-chlorophenylbiguanide (mCPBG), varenicline, 5-fluorotryptamine (5-FT), or thymol. 5-HT, 5-FT, varenicline, and mCPBG activation of 5-HT3AC, 5-HT3AD, and 5-HT3AE receptors yields similar EC50s to homomeric 5-HT3A receptors, but maximal responses differ. There are also differences in the levels of potentiation by thymol, which is greater at 5-HT3A receptors than 5-HT3AB, 5-HT3AC, 5-HT3AD...