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Critical Reviews™ in Neurobiology

ISSN Print: 0892-0915

Archives: Volume 10, 1996 to Volume 20, 2008

Critical Reviews™ in Neurobiology

DOI: 10.1615/CritRevNeurobiol.v11.i2-3.20
pages 121-142

Dopamine D2 Receptors in Signal Transduction and Behavior

Roberto Picetti
Institut de Génetique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, BP163 67404 lllkirch Cedex, C.U. de Strasbourg, France
Adolfo Saiardi
Institut de Génetique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, BP163 67404 lllkirch Cedex, C.U. de Strasbourg, France
Tarek Abdel Samad
Institut de Génetique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, BP163 67404 lllkirch Cedex, C.U. de Strasbourg, France
Yuri Bozzi
Institut de Génetique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, BP163 67404 lllkirch Cedex, C.U. de Strasbourg, France
Ja-Hyun Baik
Laboratory of Molecular Biology, Medical Research Center, College of Medicine-Yonsei University, Seoul, South Korea
Emiliana Borrelli
Institut de Génetique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, BP163 67404 lllkirch Cedex, C.U. de Strasbourg, France

ABSTRACT

The dopamine D2 receptor belongs to the family of seven transmembrane domain G-protein-coupled receptors and is highly expressed in the central nervous system and the pituitary gland. The binding of dopamine to the D2 receptor is crucial for the regulation of diverse physiological functions, such as the control of locomotor activity and the synthesis of peptide hormones. Two alternatively spliced transcripts are generated from the D2 receptor gene and code for the D2L and D2S isoforms, which are 444 and 415 amino acids in length, respectively. These isoforms 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 insertion of 29 amino acids in the putative third intracellular loop of the receptor. This loop is involved in the coupling of the receptor to different G proteins. Experiments have shown that the D2 isoforms have different 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 transduced by the binding of dopamine to D2 receptors. Important insights into D2 receptor function in vivo have been obtained by knocking out the D2 gene in mice. The Parkinsonian-like phenotype of D2-null mice demonstrates the importance of the D2 receptor for locomotor function.