Effects of reciprocal chimeras between the C‐terminal portion of third intracellular loops of the human dopamine D2 and D3 receptors

The dopamine D3 receptor is a member of the G protein-coupled superfamily of receptors. However, its coupling with intracellular events is still not well understood. We have performed chimera constructions in which amino acid residues located in a region of the receptor involved in the coupling with second messengers (the C-terminal portion of the third intracellular loop) have been exchanged between dopamine D2 and D3 receptors. Chimera constructions did not modify substantially the pharmacological profiles, nor G protein coupling, as compared to their respective wild-type receptors. However, the D2 receptor chimera, containing the C-terminal portion of the third intracellular loop of the D3 receptor, has a lower potency to inhibit cyclic AMP production. The reciprocal construction generated a D3 receptor that is fully coupled to this second messenger pathway whereas, the native D3 receptor is uncoupled to this pathway in our transfected cells. These results suggest that the sequence selected is important for specific coupling characteristics shown by these two dopamine receptor homologues.