Multiple D2 dopamine receptors produced by alternative RNA splicing

Abstract

DOPAMINE receptors belong to a large class of neurotransmitter and hormone receptors that are linked to their signal transduction pathways through guanine nucleotide binding regulatory proteins (G proteins). Pharmacological, biochemical and physiological criteria have been used to define two subcategories of dopamine receptors1 referred to as D1 and D2. D1 receptors activate adenylyl cyclase2 and are coupled with the Gs regulatory protein3. By contrast, activation of D2 receptors results in various responses including inhibition of adenylyl cyclase4, inhibition of phosphatidylinositol turnover5, increase in K+ channel activity6 and inhibition of Ca2+ mobilization7. The G protein(s) linking the D2 receptors to these responses have not been identified, although D2 receptors have been shown to both copurify8,9 and functionally reconstitute10,11 with both Gi and Go related proteins3. The diversity of responses elicited by D2-receptor activation could reflect the existence of multiple D2 receptor subtypes, the identification of which is facilitated by the recent cloning of a complementary DNA encoding a rat D2 receptor12. This receptor exhibits considerable amino-acid homology with other members of the G protein-coupled receptor superfamily12,13. Here we report the identification and cloning of a cDNA encoding an RNA splice variant of the rat D2 receptor cDNA12. This cDNA codes for a receptor isoform which is predominantly expressed in the brain, and contains an additional 29 amino acids in the third cytoplasmic loop, a region believed to be involved in G protein coupling. © 1989 Nature Publishing Group.