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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Functional and radioligand binding characterization of rat 5-HT6 receptors stably expressed in HEK293 cells.

We have stably expressed the rat 5-HT6 receptor in HEK293 cells at a density of > 2 pmol/mg protein, as determined in equilibrium binding studies with [3H]-LSD and [3H]-5-HT and compared the affinity of a range of compounds in competition binding experiments with either [3H]-LSD or [3H]-5-HT as radioligand. A variety of tryptamine derivatives were tested and showed a significantly higher affinity when the 5-HT6 receptor was labelled with [3H]-5-HT, whereas ergoline compounds and several antagonists had higher affinities when [3H]-LSD was used as radioligand. Subsequently we examined the ability of LSD, 5-HT and a number of tryptamine derivatives to stimulate cAMP accumulation in order to determine their agonist potency and efficacy. We observed the following rank order of potency: LSD > omega-N-methyl-5-HT approximately bufotenine approximately 5- methoxytryptamine > 5-HT > 2-methyl-5-HT approximately 5-benzyloxytryptamine approximately tryptamine > 5-carboxamidotryptamine > > 5-HTQ. LSD, lisuride, 2-methyl-5-HT, tryptamine and 5-benzyloxytryptamine behaved as partial agonists relative to 5-HT. The rank order of potency of the tryptamine compounds correlated well with their affinities determined in binding assays. In addition, we have tested a number of antagonists in this system (rank order of potency: methiothepin, clozapine, mianserin and ritanserin). This characterization of the pharmacological properties of recombinant 5-HT6 receptor will facilitate the identification of 5-HT6 receptor-mediated responses in physiological systems.[1]


  1. Functional and radioligand binding characterization of rat 5-HT6 receptors stably expressed in HEK293 cells. Boess, F.G., Monsma, F.J., Carolo, C., Meyer, V., Rudler, A., Zwingelstein, C., Sleight, A.J. Neuropharmacology (1997) [Pubmed]
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