DOPAMINE D2 RECEPTORS IN SIGNAL-TRANSDUCTION AND BEHAVIOR

The dopamine D2 receptor belongs to the family of seven transmembrane domain G-protein-coupled receptors and is highly expressed in the cent ral nervous system and the pituitary gland. The binding of dopamine to the D2 receptor is crucial for the regulation of diverse physiologica l functions, such as the control of locomotor activity and the synthes is of peptide hormones. Two alternatively spliced transcripts are gene rated from the D2 receptor gene and code for the D2L and D2S isoforms, which are 444 and 415 amino acids in length, respectively. These isof orms exhibit similar pharmacological characteristics and are expressed in the same cell types, with a ratio that normally favors expression of the longer isoform. The D2L isoform differs from D2S by the inserti on of 29 amino acids in the putative third intracellular loop of the r eceptor. This loop is involved in the coupling of the receptor to diff erent G proteins. Experiments have shown that the D2 isoforms have dif ferent G-protein-coupling affinities, suggesting that these receptors might serve different functions in vivo. Additionally, this difference in coupling affinity could be a mechanism to amplify the signal trans duced by the binding of dopamine to D2 receptors. Important insights i nto D2 receptor function in vivo have been obtained by knocking out th e D2 gene in mice. The Parkinsonian-like phenotype of D2-null mice dem onstrates the importance of the D2 receptor for locomotor function.