![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Howard Hughes Medical Institute and Department of Cell Biology,
Duke University Medical Center, Durham, North Carolina 27710
Despite a great deal of research, the second messenger coupling of the
dopamine D3 receptor has not yet been clearly established. The closely related D2 and D4 receptors have
been shown to inhibit adenylyl cyclase activity in a variety of cell
types, but the D3 receptor has little or no effect on this
second messenger system. We now demonstrate that when the
D3 receptor and adenylyl cyclase type V are coexpressed in
293 cells, the agonist quinpirole causes 70% inhibition of
forskolin-stimulated cAMP levels. This effect seems to be selective for
this adenylyl cyclase isoform because the D3 receptor does
not inhibit adenylyl cyclase types I or VI and only weakly stimulates
adenylyl cyclase type II. In contrast, the D2 receptor
inhibits cAMP accumulation in 293 cells in the absence of cotransfected
adenylyl cyclases and stimulates adenylyl cyclase type II to a greater
extent than the D3 receptor. The inhibition of adenylyl
cyclase type V by the D3 receptor is sensitive to pertussis
toxin, suggesting the involvement of G proteins of the Gi
family. Guanosine-5
-O-(3-thio)triphosphate binding
studies indicate that the D3 receptor weakly activates all
three Gi
subunits, whereas the D2 receptor
activates these G proteins to a substantially greater extent. However,
despite its relative inability to promote G protein activation, the
D3 receptor is capable of substantial and consistent
inhibition of adenylyl cyclase type V. The robust second messenger
coupling of the D3 receptor in a heterologous system with
defined components provides a system for further studies of the
function of this receptor and should facilitate the development and
characterization of new D3 receptor ligands.
This article has been cited by other articles:
|
|
 |
|
  C. Fiorentini, C. Busi, E. Gorruso, C. Gotti, P. Spano, and C. Missale Reciprocal Regulation of Dopamine D1 and D3 Receptor Function and Trafficking by Heterodimerization Mol. Pharmacol., July 1, 2008; 74(1): 59 - 69. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Millan, C. M. la Cour, F. Novi, R. Maggio, V. Audinot, A. Newman-Tancredi, D. Cussac, V. Pasteau, J.-A. Boutin, T. Dubuffet, et al. S33138 [N-[4-[2-[(3aS,9bR)-8-cyano-1,3a,4,9b-tetrahydro[1]-benzopyrano[3,4-c]pyrrol-2(3H)-yl)-ethyl]phenylacetamide], A Preferential Dopamine D3 versus D2 Receptor Antagonist and Potential Antipsychotic Agent: I. Receptor-Binding Profile and Functional Actions at G-Protein-Coupled Receptors J. Pharmacol. Exp. Ther., February 1, 2008; 324(2): 587 - 599. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Zeng, I. Armando, Y. Luo, G. M. Eisner, R. A. Felder, and P. A. Jose Dysregulation of dopamine-dependent mechanisms as a determinant of hypertension: studies in dopamine receptor knockout mice Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H551 - H569. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E.-Y. Cho, D.-I. Cho, J. H. Park, H. Kurose, M. G. Caron, and K.-M. Kim Roles of Protein Kinase C and Actin-Binding Protein 280 in the Regulation of Intracellular Trafficking of Dopamine D3 Receptor Mol. Endocrinol., September 1, 2007; 21(9): 2242 - 2254. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Jeanneteau, B. Funalot, J. Jankovic, H. Deng, J.-P. Lagarde, G. Lucotte, and P. Sokoloff A functional variant of the dopamine D3 receptor is associated with risk and age-at-onset of essential tremor PNAS, July 11, 2006; 103(28): 10753 - 10758. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-Y. Kao, H.-L. Lai, M.-J. Hwang, and Y. Chern An Important Functional Role of the N Terminus Domain of Type VI Adenylyl Cyclase in G{alpha}i-mediated Inhibition J. Biol. Chem., August 13, 2004; 279(33): 34440 - 34448. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Zeng, D. Wang, Z. Yang, Z. Wang, L. D. Asico, C. S. Wilcox, G. M. Eisner, W. J. Welch, R. A. Felder, and P. A. Jose Dopamine D1 Receptor Augmentation of D3 Receptor Action in Rat Aortic or Mesenteric Vascular Smooth Muscles Hypertension, March 1, 2004; 43(3): 673 - 679. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. F. Agnati, S. Ferre, C. Lluis, R. Franco, and K. Fuxe Molecular Mechanisms and Therapeutical Implications of Intramembrane Receptor/Receptor Interactions among Heptahelical Receptors with Examples from the Striatopallidal GABA Neurons Pharmacol. Rev., September 1, 2003; 55(3): 509 - 550. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Cussac, A. Newman-Tancredi, V. Pasteau, and M. J. Millan Human Dopamine D3 Receptors Mediate Mitogen-Activated Protein Kinase Activation Via a Phosphatidylinositol 3-Kinase and an Atypical Protein Kinase C-Dependent Mechanism Mol. Pharmacol., November 1, 1999; 56(5): 1025 - 1030. [Abstract] [Full Text]
|
|
|
|
|
|
M. H. Ghahremani, P. Cheng, P. M. C. Lembo, and P. R. Albert Distinct Roles for Galpha i2, Galpha i3, and Gbeta gamma in Modulation of Forskolin- or Gs-mediated cAMP Accumulation and Calcium Mobilization by Dopamine D2S Receptors J. Biol. Chem., April 2, 1999; 274(14): 9238 - 9245. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. V. Kuzhikandathil and G. S. Oxford Activation of Human D3 Dopamine Receptor Inhibits P/Q-Type Calcium Channels and Secretory Activity in AtT-20 Cells J. Neurosci., March 1, 1999; 19(5): 1698 - 1707. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Newman-Tancredi, D. Cussac, V. Audinot, V. Pasteau, S. Gavaudan, and M. J. Millan G Protein Activation by Human Dopamine D3 Receptors in High-Expressing Chinese Hamster Ovary Cells: A Guanosine-5'-O-(3-[35S]thio)-Triphosphate Binding and Antibody Study Mol. Pharmacol., March 1, 1999; 55(3): 564 - 574. [Abstract] [Full Text]
|
|
|
|
|
|
M. Scarselli, F. Novi, E. Schallmach, R. Lin, A. Baragli, A. Colzi, N. Griffon, G. U. Corsini, P. Sokoloff, R. Levenson, et al. D2/D3 Dopamine Receptor Heterodimers Exhibit Unique Functional Properties J. Biol. Chem., August 3, 2001; 276(32): 30308 - 30314. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-M. Kim, K. J. Valenzano, S. R. Robinson, W. D. Yao, L. S. Barak, and M. G. Caron Differential Regulation of the Dopamine D2 and D3 Receptors by G Protein-coupled Receptor Kinases and beta -Arrestins J. Biol. Chem., September 28, 2001; 276(40): 37409 - 37414. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
