Dopamine Receptor Homooligomers and Heterooligomers in Schizophrenia

被引:29
作者
Perreault, Melissa L. [1 ,3 ]
O'Dowd, Brian F. [1 ,3 ]
George, Susan R. [1 ,2 ,3 ]
机构
[1] Univ Toronto, Dept Pharmacol, Toronto, ON M5S 1A8, Canada
[2] Univ Toronto, Dept Med, Toronto, ON M5S 1A8, Canada
[3] Ctr Addict & Mental Hlth, Toronto, ON, Canada
关键词
Dimers; Dopamine receptors; Heteromers; Homomers; Schizophrenia; ADENOSINE A(2A) RECEPTORS; HIGH-AFFINITY STATE; CARD-SORTING-TEST; PREFRONTAL CORTEX; ANTIPSYCHOTIC-DRUG; DIHYDREXIDINE DAR-0100; TREATING SCHIZOPHRENIA; HETERO-DIMERIZATION; NEUROTROPHIC FACTOR; GLUTAMATE AGONISTS;
D O I
10.1111/j.1755-5949.2010.00228.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
P>Over the past two decades the dopamine D2 receptor has been undoubtedly the most widely studied dopamine receptor for the therapeutic treatment of schizophrenia, as the majority of antipsychotics exhibit antagonism at this receptor. However, the cognitive symptoms of the disorder are mostly resistant to the majority of available antipsychotic treatments and, as a result, there is a critical need to develop novel therapies that ameliorate all symptoms. The recognition that dopamine receptors, such as all G protein-coupled receptors (GPCRs), exist as oligomeric complexes has provided new avenues for drug design in the search for novel therapies. Furthermore, that it is now known that dopamine receptors can form heteromers, such as the dopamine D1-D2 receptor heteromer, with pharmacology and function distinct from its constituent receptors, has significantly expanded the range of potential drug targets. The aim of this review is to discuss the therapeutic relevance of these dopamine receptor oligomers to schizophrenia and to address the potential value of dopamine receptor heteromers in the search for new therapeutic strategies.
引用
收藏
页码:52 / 57
页数:6
相关论文
共 118 条
[81]  
MOTTOLA DM, 1992, J PHARMACOL EXP THER, V262, P383
[82]   A single 20 mg dose of the full D1 dopamine agonist dihydrexidine (DAR-0100) increases prefrontal perfusion in schizophrenia [J].
Mu, Qiwen ;
Johnson, Kevin ;
Morgan, Paul S. ;
Grenesko, Emily L. ;
Molnar, Christine E. ;
Anderson, Berry ;
Nahas, Ziad ;
Kozel, F. Andrew ;
Kose, Samet ;
Knable, Michael ;
Fernandes, Prabhavathi ;
Nichols, David E. ;
Mailman, Richard B. ;
George, Mark S. .
SCHIZOPHRENIA RESEARCH, 2007, 94 (1-3) :332-341
[83]   The antipsychotic potential of l-stepholidine -: a naturally occurring dopamine receptor D1 agonist and D2 antagonist [J].
Natesan, Sridhar ;
Reckless, Greg E. ;
Barlow, Karen B. L. ;
Odontiadis, John ;
Nobrega, Jose N. ;
Baker, Glen B. ;
George, Susan R. ;
Mamo, David ;
Kapur, Shitij .
PSYCHOPHARMACOLOGY, 2008, 199 (02) :275-289
[84]   ACTIVATION OF CALCIUM/CALMODULIN-DEPENDENT PROTEIN KINASE IIα IN THE STRIATUM BY THE HETEROMERIC D1-D2 DOPAMINE RECEPTOR COMPLEX [J].
Ng, J. ;
Rashid, A. J. ;
So, C. H. ;
O'Dowd, B. F. ;
George, S. R. .
NEUROSCIENCE, 2010, 165 (02) :535-541
[85]   Hyperactive Mice Show Elevated D2High Receptors, A Model for Schizophrenia: Calcium/Calmodulin-Dependent Kinase II Alpha Knockouts [J].
Novak, Gabriela ;
Seeman, Philip .
SYNAPSE, 2010, 64 (10) :794-800
[86]   Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized Phase 2 clinical trial [J].
Patil, Sandeep T. ;
Zhang, Lu ;
Martenyi, Ferenc ;
Lowe, Stephen L. ;
Jackson, Kimberley A. ;
Andreev, Boris V. ;
Avedisova, Alla S. ;
Bardenstein, Leonid M. ;
Gurovich, Issak Y. ;
Morozova, Margarita A. ;
Mosolov, Sergey N. ;
Neznanov, Nikolai G. ;
Reznik, Alexander M. ;
Smulevich, Anatoly B. ;
Tochilov, Vladimir A. ;
Johnson, Bryan G. ;
Monn, James A. ;
Schoepp, Darryle D. .
NATURE MEDICINE, 2007, 13 (09) :1102-1107
[87]  
PEHEK EA, 1994, J NEUROCHEM, V63, P2118
[88]   D1-D2 dopamine receptor heterooligomers with unique pharmacology are coupled to rapid activation of Gq/11 in the striatum [J].
Rashid, Asim J. ;
So, Christopher H. ;
Kong, Michael M. C. ;
Furtak, Teresa ;
El-Ghundi, Mufida ;
Cheng, Regina ;
O'Dowd, Brian F. ;
George, Susan R. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (02) :654-659
[89]  
Riehemann S, 2001, EUR ARCH PSY CLIN N, V251, P66, DOI 10.1007/s004060170055
[90]   Adenosine A(2A) agonists: A potential new type of atypical antipsychotic [J].
Rimondini, R ;
Ferre, S ;
Ogren, SO ;
Fuxe, K .
NEUROPSYCHOPHARMACOLOGY, 1997, 17 (02) :82-91