TY - JOUR
T1 - The neurobiology of dopamine receptors
T2 - Evolution from the dual concept to heterodimer complexes
AU - Missale, Cristina
AU - Fiorentini, Chiara
AU - Collo, Ginetta
AU - Spano, Pierfranco
PY - 2010/10
Y1 - 2010/10
N2 - Context: G protein-coupled receptors (GPCRs) have been classically thought to work as monomeric entities. The current view of their organization, however, assumes that they are part of highly organized molecular complexes, where different receptors and interacting proteins are clustered. These heteromers have peculiar pharmacological, signaling, and trafficking properties. GPCR heteromerization, raising different combinatorial possibilities, thus underlies an unexpected level of diversity within this receptor family. Methods: In this paper, we summarize recent data, reported by different research groups, suggesting that the dopamine (DA) D1 receptor forms heteromers with receptors of the same family and with structurally and functionally divergent receptors. Results and discussion: DA D1 and D3 receptors and glutamate NMDA receptors regulate rewarding mechanisms and motivated behavior, modulate emotional and cognitive processes and regulate locomotor activity by extensive cross-talk mechanisms. Co-localization of D1 and D3 receptors and D1 and NMDA receptors in specific neuronal populations in the striatum and nucleus accumbens, moreover, suggested that their cross-talk may involve direct interactions. By using different experimental approaches various groups have, in fact, demonstrated the existence of D1-NMDA and D1-D3 heteromers, in both transfected cell systems and in the straitum, with peculiar pharmacological, signaling, and functional properties. The putative role of the D1-D3 and D1-NMDA heteromers in the physiological regulation of striatal function and in the development of motor dysfunctions will be discussed.
AB - Context: G protein-coupled receptors (GPCRs) have been classically thought to work as monomeric entities. The current view of their organization, however, assumes that they are part of highly organized molecular complexes, where different receptors and interacting proteins are clustered. These heteromers have peculiar pharmacological, signaling, and trafficking properties. GPCR heteromerization, raising different combinatorial possibilities, thus underlies an unexpected level of diversity within this receptor family. Methods: In this paper, we summarize recent data, reported by different research groups, suggesting that the dopamine (DA) D1 receptor forms heteromers with receptors of the same family and with structurally and functionally divergent receptors. Results and discussion: DA D1 and D3 receptors and glutamate NMDA receptors regulate rewarding mechanisms and motivated behavior, modulate emotional and cognitive processes and regulate locomotor activity by extensive cross-talk mechanisms. Co-localization of D1 and D3 receptors and D1 and NMDA receptors in specific neuronal populations in the striatum and nucleus accumbens, moreover, suggested that their cross-talk may involve direct interactions. By using different experimental approaches various groups have, in fact, demonstrated the existence of D1-NMDA and D1-D3 heteromers, in both transfected cell systems and in the straitum, with peculiar pharmacological, signaling, and functional properties. The putative role of the D1-D3 and D1-NMDA heteromers in the physiological regulation of striatal function and in the development of motor dysfunctions will be discussed.
KW - D1 receptor
KW - D3 receptor
KW - L-DOPA-induced dyskinesia
KW - NMDA receptor
KW - Parkinson's disease
KW - Striatum
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U2 - 10.3109/10799893.2010.506192
DO - 10.3109/10799893.2010.506192
M3 - Article
C2 - 20684667
AN - SCOPUS:77957042248
VL - 30
SP - 347
EP - 354
JO - Journal of Receptor and Signal Transduction Research
JF - Journal of Receptor and Signal Transduction Research
SN - 1079-9893
IS - 5
ER -