Chimeric D2/D3 dopamine receptors efficiently inhibit adenylyl cyclase in HEK 293 cells.

Journal Article (Journal Article)

Despite a high degree of sequence homology, the dopamine D2 and D3 receptors have substantially different second messenger coupling properties. We have used chimeric D2/D3 receptors to investigate the contribution of the intracellular loops to the signaling properties of these receptors. In HEK 293 cells, D2 receptors inhibit prostaglandin E1-stimulated cyclic AMP levels by >90%, whereas D3 receptors inhibit cyclic AMP accumulation by only 20%. In chimeras that have the second or third intracellular loop, or both loops simultaneously, switched between the D2 and D3 receptors, the maximal inhibition of adenylyl cyclase is 60-90%. In addition, the potency of quinpirole to inhibit adenylyl cyclase activity at some of the chimeras is altered compared with the wild-type receptors. It appears that the intracellular loops of the D3 receptor are capable of interacting with G proteins, as when these loops are expressed in the D2 receptor, the chimeras inhibit adenylyl cyclase similarly to the wild-type D2 receptor. Our data suggest that the overall conformation of the D3 receptor may be such that it interacts with G proteins only weakly, but when the intracellular loops are expressed in another context or the D3 receptor structure is altered by the introduction of D2 receptor sequence, this constraint may be lifted.

Full Text

Duke Authors

Cited Authors

  • Robinson, SW; Caron, MG

Published Date

  • July 1996

Published In

Volume / Issue

  • 67 / 1

Start / End Page

  • 212 - 219

PubMed ID

  • 8666994

International Standard Serial Number (ISSN)

  • 0022-3042

Digital Object Identifier (DOI)

  • 10.1046/j.1471-4159.1996.67010212.x


  • eng

Conference Location

  • England