Oxytocin and vasopressin V1a and V2 receptors form constitutive homo- and heterodimers during biosynthesis

Mol Endocrinol. 2003 Apr;17(4):677-91. doi: 10.1210/me.2002-0222. Epub 2002 Dec 23.

Abstract

G protein-coupled receptor (GPCR) oligomerization is a growing concept that has emerged from several studies suggesting that GPCRs can form both homo- and heterodimers. Using both coimmunoprecipitation and bioluminescence resonance energy transfer (BRET) approaches, we established that the vasopressin V1a, V2, and the oxytocin receptors exist as homo- and hetero-dimers in transfected human embryonic kidney 293T cells. Each receptor protomer had a similar propensity to form homo- and heterodimers, indicating that their relative expression levels may determine the homo-/heterodimer ratio. The finding that immature forms of the receptor can be immunoprecipitated as homo- and heterodimers and the detection by BRET of such oligomer in endoplasmic reticulum-enriched fractions suggest that the oligomerization processes take place early during biosynthesis. Treatment with agonists or antagonists did not modify the BRET among any of the vasopressin and oxytocin receptor pairs studied, indicating that the dimerization state of the receptors is not regulated by ligand binding once they have reached the cell surface. Taken together, these results strongly support the notion that GPCR dimerization is a constitutive process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antidiuretic Hormone Receptor Antagonists
  • Biophysics / methods
  • Cells, Cultured
  • Dimerization
  • Humans
  • Kidney / cytology
  • Kidney / drug effects
  • Kidney / embryology
  • Ligands
  • Luminescent Measurements
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Morpholines / pharmacology
  • Precipitin Tests
  • Receptors, Oxytocin / biosynthesis*
  • Receptors, Oxytocin / genetics
  • Receptors, Oxytocin / metabolism
  • Receptors, Vasopressin / agonists
  • Receptors, Vasopressin / biosynthesis*
  • Receptors, Vasopressin / genetics
  • Receptors, Vasopressin / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction
  • Spiro Compounds / pharmacology
  • Subcellular Fractions

Substances

  • Antidiuretic Hormone Receptor Antagonists
  • Ligands
  • Luminescent Proteins
  • Morpholines
  • Receptors, Oxytocin
  • Receptors, Vasopressin
  • Recombinant Fusion Proteins
  • Spiro Compounds
  • satavaptan