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Pharmacology and biochemistry of dopamine receptors in the central nervous system and peripheral tissue.

A body of experimental and clinical data was generated over the last decade and now constitutes the basis for a new level of categorization of central dopamine (DA) receptors. Pharmacological and biochemical criteria were used in particular in our laboratories to separate those DA receptors which are linked in a stimulatory way to the enzyme adenylate cyclase and those which are not. We have indeed defined D1 and D2 receptors those DA receptors associated or unassociated to the generation of cyclic AMP, respectively. It should be stressed that the studies on DA receptors in the central nervous system and peripheral tissue were greatly facilitated following the discovery of specific agonist and antagonist drugs for the different DA receptors. As originally proposed by our group, DAergic ergot derivatives and substituted benzamides are now generally accepted as classes of drugs, endowed with agonist and antagonist properties, respectively, on DA D2 receptors. Taking into account the intracellular modifications following the interaction between DA and its own recognition sites, it can be suggested that in cerebral and peripheral tissue the recognition sites for DA are coupled to various of amplifier systems with different molecular mechanisms. According to the data presented and discussed in the text, DA D1 recognition sites appear to be linked to adenylate cyclase through a G/F protein (Ns unit) in a stimulatory way whereas DA D2 recognition sites are associated with adenylate cyclase through a G/F protein (Ns unit) in an inhibitory way or, at least in pituitary, are functionally coupled with inhibition of calcium entry into the cells.