Dopamine Receptors

It was not until the late 1950’s that dopamine was recognised as a neurotransmitter in its own right when the demonstration of its non-uniform distribution in the brain suggested a specific functional role for dopamine. Interest in dopamine was intensified by the realisation that dopamine had an important role in the pathogenesis or drug treatment of certain brain History diseases e.g. Parkinson’s disease, schizophrenia. This lead to much research on the sites of action of dopamine, the dopamine receptors. A milestone in this was the suggestion, based on anatomical, electrophysiological and pharmacological studies by Cools and Van Rossum, that there might be more than one kind of receptor for dopamine in the brain. In the 1970’s, biochemical studies on dopamine receptors based on second messenger assays, e.g. stimulation of cAMP production, and based on ligand binding assays supported the idea of more than one kind of dopamine receptor. This idea was given a firm foundation by Kebabian and Calne in their 1979 review, in which they extended an earlier suggestion by Spano, and proposed that there were two classes of dopamine receptor, D and D , with different biochemical and pharmacological properties and mediating different physiological functions. Some of the properties of these two subtypes are summarised in Table 1. Selective agonists and antagonists exist to define the two subtypes in functional assays and some of these are shown in Table 1. Both the D and D subtypes are G-protein coupled receptors but 1