Functional and Radioligand Binding Characterization of Rat 5-HT 6 Receptors Stably Expressed in HEK293 Cells

Functional and Radioligand Binding Characterization of Rat 5-HT 6 Receptors Stably Expressed in... We have stably expressed the rat 5-HT 6 receptor in HEK293 cells at a density of >2 pmol/mg protein, as determined in equilibrium binding studies with ( 3 H)-LSD and ( 3 H)-5-HT and compared the affinity of a range of compounds in competition binding experiments with either ( 3 H)-LSD or ( 3 H)-5-HT as radioligand. A variety of tryptamine derivatives were tested and showed a significantly higher affinity when the 5-HT 6 receptor was labelled with ( 3 H)-5-HT, whereas ergoline compounds and several antagonists had higher affinities when ( 3 H)-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 > ω- N -methyl-5-HT ≈ bufotenine ≈ 5-methoxytryptamine > 5-HT > 2-methyl-5-HT ≈ 5-benzyloxytryptamine ≈ tryptamine > 5-carboxamido-methoxytryptamine > 5-HT > 2-methyl-5-HT ≈ 5-benzyloxytryptamine ≈ 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-HT 6 receptor will facilitate the identification of 5-HT 6 receptor-mediated responses in physiological systems. © 1997 Elsevier Science Ltd. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neuropharmacology Elsevier

Functional and Radioligand Binding Characterization of Rat 5-HT 6 Receptors Stably Expressed in HEK293 Cells

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Publisher
Elsevier
Copyright
Copyright © 1997 Elsevier Science Ltd
ISSN
0028-3908
eISSN
1873-7064
DOI
10.1016/S0028-3908(97)00019-1
Publisher site
See Article on Publisher Site

Abstract

We have stably expressed the rat 5-HT 6 receptor in HEK293 cells at a density of >2 pmol/mg protein, as determined in equilibrium binding studies with ( 3 H)-LSD and ( 3 H)-5-HT and compared the affinity of a range of compounds in competition binding experiments with either ( 3 H)-LSD or ( 3 H)-5-HT as radioligand. A variety of tryptamine derivatives were tested and showed a significantly higher affinity when the 5-HT 6 receptor was labelled with ( 3 H)-5-HT, whereas ergoline compounds and several antagonists had higher affinities when ( 3 H)-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 > ω- N -methyl-5-HT ≈ bufotenine ≈ 5-methoxytryptamine > 5-HT > 2-methyl-5-HT ≈ 5-benzyloxytryptamine ≈ tryptamine > 5-carboxamido-methoxytryptamine > 5-HT > 2-methyl-5-HT ≈ 5-benzyloxytryptamine ≈ 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-HT 6 receptor will facilitate the identification of 5-HT 6 receptor-mediated responses in physiological systems. © 1997 Elsevier Science Ltd.

Journal

NeuropharmacologyElsevier

Published: Apr 1, 1997

References

  • Effects of altered 5-HT 6 expression in the rat: functional studies using antisense oligonucleotides
    Sleight, A.J.; Monsma, F.J.; Borroni, E.; Austin, R.H.; Bourson, A.

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