[3H]5-hydroxytryptamine labels the agonist high affinity state of the cloned rat 5-HT4 receptor.
We have used the cloned rat 5-HT4 receptor, and determined that the single protein product produced is able to bind both [3H]5-HT and [3H]GR113808 ([1-[(2-methyl sulphonyl) amino] ethyl-4-piperidinyl] methyl-1-methyl-1H-indole-3-carboxylate) with high affinity. The affinities of agonists for the [3H]5-HT (agonist)-labelled receptor were significantly higher than for the [3H]GR113808 (antagonist)-labelled receptor. Furthermore, [3H]5-HT binding was reduced by addition of guanyl nucleotides. These results strongly support the hypothesis that the 5-HT4 receptor displays two interconvertible affinity states (high and low) for agonists, characteristic of many G protein coupled receptors. [3H]5-HT, at the concentration employed, therefore labels the agonist high affinity state of the 5-HT4 receptor in systems in which high densities of this receptor are found.
Adham
N
N
Synaptic Pharmaceutical Corporation, Paramus, NJ 07652, USA.
Gerald
C
C
Schechter
L
L
Vaysse
P
P
Weinshank
R
R
Branchek
T
T
D000345:Affinity Labels / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D019556:COS Cells; D003001:Cloning, Molecular; D007211:Indoles / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism*; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000378:metabolism; D013449:Sulfonamides / Q000378:metabolism; D014162:Transfection
D000345:Affinity Labels; D007211:Indoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin; C082871:GR 113808