Characterization of recombinant human serotonin 5HT1A receptors expressed in Chinese hamster ovary cells. [3H]spiperone discriminates between the G-protein-coupled and -uncoupled forms

Biochem Pharmacol. 1993 Mar 9;45(5):1003-9. doi: 10.1016/0006-2952(93)90243-p.

Abstract

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / metabolism
  • Animals
  • CHO Cells
  • Cricetinae
  • GTP-Binding Proteins / metabolism*
  • Guanosine Triphosphate / pharmacology
  • Humans
  • Radioligand Assay
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / metabolism*
  • Recombinant Proteins / metabolism
  • Serotonin Antagonists
  • Spiperone / metabolism*
  • Tritium

Substances

  • Receptors, Serotonin
  • Recombinant Proteins
  • Serotonin Antagonists
  • Tritium
  • Spiperone
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Guanosine Triphosphate
  • GTP-Binding Proteins