Human dopamine D1 receptor encoded by an intronless gene on chromosome 5

Abstract

RECEPTORS for dopamine have been classified into two functional types, D1 and D2 (refs 1,2). They belong to the family of receptors acting through G (or guanine nucleotide-binding) proteins3. D2 receptors inhibit adenylyl cyclase, but D1 receptors stimulate adenylyl cyclase and activate cyclic AMP-dependent protein kinases4,5. Dopamine D1 and D2 receptors are targets of drug therapy in many psychomotor disorders, including Parkinson's disease and schizophrenia6,7, and may also have a role in drug addiction and alchoholism8. D1 receptors regulate neuron growth and differentiation9, influence behaviour and modify dopamine D2 receptor-mediated events10,11. We report here the cloning of the D1 receptor gene, which resides on an intronless region on the long arm of chromosome 5, near two other members of the G-linked receptor family. The expressed protein, encoded by 446 amino acids, binds drugs with affinities identical to the native human D1 receptor. The presence of a D1 receptor gene restriction fragment length polymorphism will be helpful for future disease linkage studies.