Delineation of the conserved functional properties of D1A, D1B and D1C dopamine receptor subtypes in vertebrates.

• Published in: Biology of the Cell
• Main Authors: Le Crom, Stéphane, Sugamori, Kim S, Sidhu, Anita, Niznik, Hyman B, Vernier, Philippe
• Other Authors: Développement, évolution et plasticité du système nerveux (DEPSN), Centre National de la Recherche Scientifique (CNRS), Institut de Neurobiologie Alfred Fessard (INAF), Laboratory of Molecular Neurobiology, Center For Addiction and Mental Health, Laboratory of Molecular Neurochemistry, Department of Pediatrics, Georgetown University
• Format: Article in Journal/Newspaper
• Language: English
• Published: HAL CCSD 2004
• Subjects: MESH: Animals; MESH: COS Cells; MESH: Phylogeny; MESH: Protein Binding; MESH: Protein Structure; Tertiary; MESH: Receptors; Dopamine D1; Dopamine D5; MESH: Time Factors; MESH: Transfection; MESH: Xenopus; MESH: Xenopus laevis; MESH: Cyclic AMP; MESH: Databases; MESH: Dopamine; MESH: Evolution; MESH: Fishes; MESH: Humans; MESH: Kinetics; MESH: Ligands; [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]; Anguilla anguilla
• Online Access: https://hal.archives-ouvertes.fr/hal-00121753; https://doi.org/10.1016/j.biolcel.2004.03.002

The three main subtypes of dopamine D(1) receptor (D(1A), D(1B) and D(1C)) subtypes found in most vertebrate groups were generated by two major steps of gene duplications, early in evolution. To identify the functional characteristics contributing to conservation of these paralogous D(1) receptors in vertebrates, the pharmacological and functional properties of fish (Anguilla anguilla), amphibian (Xenopus laevis) and human receptors were systematically analysed in transfected cells. The ligand-binding parameters appeared essentially similar for orthologous receptors, but differed significantly among the subtypes. The D(1A) receptors from the three species displayed low intrinsic activity and a fast rate of agonist-induced desensitization. All the orthologous D(1B) receptors exhibited a similar desensitization time-course, but with smaller amplitude of decrease than D(1A) receptors, in agreement with their higher basal activity. In contrast, D(1C) receptors, which do not exist in mammals, have low intrinsic activity and exhibit only weak, but rapid, agonist-induced desensitization, without any changes upon longer treatment with agonist. Thus, each of the three D(1) receptor subtypes are characterized by activation and desensitization properties, in a sequence-specific manner, which has been probably acquired early after gene duplications, and constrained their conservation during vertebrate evolution. These properties have been instrumental to adapt dopamine system to the physiology of the numerous neuronal networks and functions they control in the large and complex brains of vertebrates.