[The molecular biology of dopamine receptors]

Abstract

In this article advances in the molecular biology of dopamine receptors are reviewed. Dopamine receptor subtypes D1, D2 and D3 have been cloned and characterized over the last three years. Analysis of their amino acid sequences has shown that these subtypes belong to the G protein-coupled receptor family, with seven transmembrane domains, a C-terminus within the cell and a N-terminus outside the cell. The distribution of mRNAs coding these receptors was determined by Northern blotting or in situ hybridization, and they were expressed in eukaryotic cells for application in such pharmacological experiments as receptor binding and cAMP accumulation. D1 receptors, which have 446 amino acids, were expressed in cells and detected by [3H]SCH23390 binding and cAMP accumulation assay. However, another paper described D1 as having 485 amino acids and suggested the existence of D1 receptor subclasses. D2 receptors have two isoforms, D2 (444) and D2(415), produced by alternative RNA splicing. D2 (444) has 29 additional amino acids in the third intracellular loop of D2(415). The mRNA distribution differs between D2 (444) and D2 (415), although the pharmacological profiles of the two isoforms are identical. The D3 receptor is localized in the limbic area of the brain and has a relatively high affinity for atypical neuroleptics and putative autoreceptor-selective agents. D3 appears to mediate some of the antipsychotic effects of the agents.