Two sites in the third inner loop of the dopamine D2 receptor are involved in functional G protein-mediated coupling to adenylate cyclase

FEBS Lett. 1993 Jul 5;325(3):215-9. doi: 10.1016/0014-5793(93)81076-c.

Abstract

Synthetic peptides, corresponding to the amino acid sequences of the N- and C-terminal parts of the 3rd intracellular loop of the dopamine D2 receptor, attenuate dopaminergic adenylate cyclase inhibition in membranes. Both peptides also activate directly GTPase activity in membranes. We suggest a functional model for G(i)-coupled receptors where two sites in the 3rd inner loop compose the links for the receptor-G protein interaction thus providing the tools for a selective and adjustable response. Functional coupling was not affected by a peptide representing the insert in the long form of the dopamine D2 receptor (D2(long)). The selectivity pattern of conventional G protein-linked receptors also sheds some light on the recently observed interaction of beta-amyloid protein precursor (APP) complexes with G proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclase Inhibitors
  • Adenylyl Cyclases / metabolism*
  • Amino Acid Sequence
  • Cell Line
  • Cell Membrane / enzymology
  • GTP Phosphohydrolases / metabolism
  • GTP-Binding Proteins / metabolism*
  • Humans
  • Molecular Sequence Data
  • Receptors, Dopamine D2 / chemistry
  • Receptors, Dopamine D2 / metabolism*

Substances

  • Adenylyl Cyclase Inhibitors
  • Receptors, Dopamine D2
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • Adenylyl Cyclases