An N-terminal dopamine D(2s) receptor clone was constructed and coexpressed in COS-7 cells together with a separate gene fragment coding for the C-terminal sequence of the dopamine D(2s) receptor. The truncated receptor (referred to as D(2trunc)) contained transmembrane domains I-V and the N-terminal portion of the third cytoplasmic loop, whereas the C-terminal receptor fragment (referred to as D(2tail)) contained transmembrane domains VI and VII and the adjacent intra- and extracellular sequences of the dopamine D(2s) receptor. Expression in COS-7 cells of either of these two polypeptides alone did not result in any detectable [3H]methylspiperone binding activity. However, specific [3H]methylspiperone binding could be observed after coexpression of the D(2trunc) and D(2tail) gene constructs; the number of receptors present on the plasma membrane was about 10% with respect to that of the wild type. The binding properties of the coexpressed fragments were similar to those of the wild-type dopamine D(2s) receptor for agonists and antagonists. Functional stimulation of the cotransfected D(2trunc) and D(2tail) fragments with quinpirole resulted in the inhibition of adenylate cyclase activity. Maximal inhibition corresponds to a 28% decrease in forskolin-stimulated adenylate cyclase. The apparent IC(50) of quinpirole was 5.1+/-0.3 mcM. These findings confirm and extend analogous data for other G protein-coupled receptors and indicate that this phenomenon is of general importance for the entire family of these proteins.