Characterization of recombinant human serotonin 5HT1A receptors expressed in Chinese hamster ovary cells. [3H]spiperone discriminates between the G-protein-coupled and -uncoupled forms.
5HT1A serotonin (5-hydroxytryptamine) receptors have been characterized by ligand binding in a recombinant Chinese Hamster Ovary cell line expressing the human receptor gene. The agonist ligand [3H]2-(N,N-dipropylamino)-8-hydroxy-1,2,3,4-tetrahydronaphthalene ([3H]8-OH-DPAT) and the antagonist [3H]spiperone were used. For both radioligands the binding sites labelled have the properties of 5HT1A receptors and most antagonists show roughly equal affinities for the receptors labelled by either [3H]8-OH-DPAT or [3H]spiperone. Agonists, however, show higher affinities for the sites labelled by [3H]8-OH-DPAT and the antagonist spiperone conversely shows a higher affinity for the sites labelled by [3H]spiperone. Whereas [3H]8-OH-DPAT binding is inhibited by guanosine triphosphate (GTP) the binding of [3H]spiperone is increased by GTP. A model is proposed for the results whereby [3H]8-OH-DPAT labels a form of the receptor coupled to a G-protein and [3H]spiperone labels a form of the receptor uncoupled from G-proteins (or possibly coupled to a different G-protein).
Sundaram
H
H
Biological Laboratory, The University, Canterbury, Kent, U.K.
Newman-Tancredi
A
A
Strange
P G
PG
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006801:Humans; D011869:Radioligand Assay; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012702:Serotonin Antagonists; D013134:Spiperone / Q000378:metabolism*; D014316:Tritium
D011985:Receptors, Serotonin; D011994:Recombinant Proteins; D012702:Serotonin Antagonists; D014316:Tritium; D013134:Spiperone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins