Augmentation of receptor-mediated adenylyl cyclase activity by Gi-coupled prostaglandin receptor subtype EP3 in a Gbetagamma subunit-independent manner

Biochem Biophys Res Commun. 2002 Jan 11;290(1):162-8. doi: 10.1006/bbrc.2001.6169.

Abstract

We previously demonstrated that the mouse EP3beta receptor and its C-terminal tail-truncated receptor (abbreviated T-335) expressed in Chinese hamster ovary cells showed agonist-dependent and fully constitutive Gi activity in forskolin-stimulated cAMP accumulation, respectively. Here we examined the effect of the EP3beta receptor or T-335 receptor on adenylyl cyclase activity stimulated by the Gs-coupled EP2 subtype receptor in COS-7 cells. As a result, sulprostone, a selective EP3 agonist, dose dependently augmented butaprost-stimulated adenylyl cyclase activity in EP3beta receptor- or T-335 receptor-expressing COS-7 cells. However, such adenylyl cyclase augmentation was not attenuated by either pertussis toxin treatment or expression of the PH domain of rat betaARK1, which serves as a scavenger of Gbetagamma subunits, but was partially attenuated by treatment with either 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl)ester, an intracellular Ca(2+) chelator, or W-7, a calmodulin inhibitor. These findings suggest that the C-terminal tail of the EP3beta receptor is not essentially involved in activation of EP2 receptor-stimulated adenylyl cyclase in a Ca(2+)/calmodulin-dependent but Gbetagamma subunit-independent manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / metabolism
  • Adenylate Cyclase Toxin
  • Adenylyl Cyclases / metabolism*
  • Alprostadil / analogs & derivatives*
  • Alprostadil / pharmacology
  • Animals
  • COS Cells
  • Calcium / metabolism
  • Calmodulin / metabolism
  • Cell Membrane / metabolism
  • Chelating Agents / pharmacology
  • Cloning, Molecular
  • Cyclic AMP / metabolism
  • DNA, Complementary / metabolism
  • Dinoprostone / analogs & derivatives*
  • Dinoprostone / pharmacology
  • Dose-Response Relationship, Drug
  • Egtazic Acid / analogs & derivatives*
  • Egtazic Acid / pharmacology
  • Enzyme Inhibitors / pharmacology
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism*
  • Pertussis Toxin
  • Prostaglandins / metabolism*
  • Prostaglandins E, Synthetic / pharmacology
  • Protein Structure, Tertiary
  • Rats
  • Receptors, Prostaglandin E / metabolism*
  • Receptors, Prostaglandin E, EP3 Subtype
  • Sulfonamides / pharmacology
  • Virulence Factors, Bordetella / pharmacology

Substances

  • Adenylate Cyclase Toxin
  • Calmodulin
  • Chelating Agents
  • DNA, Complementary
  • Enzyme Inhibitors
  • Prostaglandins
  • Prostaglandins E, Synthetic
  • Ptger3 protein, mouse
  • Ptger3 protein, rat
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP3 Subtype
  • Sulfonamides
  • Virulence Factors, Bordetella
  • sulprostone
  • Egtazic Acid
  • Adenosine Diphosphate
  • W 7
  • Cyclic AMP
  • Pertussis Toxin
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • Adenylyl Cyclases
  • Alprostadil
  • butaprost
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
  • Dinoprostone
  • Calcium