Abstract
Dopamine and glutamate have been shown to extensively interact in the striatum, nucleus accumbens, hippocampus and prefrontal cortex, to regulate different physiological functions, including locomotor activity, positive reinforcement, attention and working memory. Although dysfunctions of dopamine transmission have long been identified as critical determinants of neurological and neuropsychiatric disorders, such as Parkinsons disease and schizophrenia, there is now increasing evidence that concurrent alterations of dopamine and glutamate function may play a central role in the pathophysiology of these diseases. Thus, defining the characteristics of dopamine-glutamate interactions may be crucial to identify alternative molecular targets for the development of novel pharmacological tools. At the postsynaptic level, interactions between the dopamine D1 and the glutamate NMDA receptors appear to be particularly relevant. Different mechanisms are involved in this interactions: 1) D1R-dependent, second messenger-mediated phosphorylation of NMDAR subunits; 2) coordinated regulation of receptor trafficking at synaptic sites; 3) formation of an heteromeric D1/NMDA receptor complex. In this paper we review the molecular mechanisms, functional implications and pharmacological significance of D1R/NMDAR interaction via direct protein-protein oligomerization.
Keywords: glutamate transmission, cAMP-PKA pathway, bioluminescence resonance energy transfer (BRET), NMDA-mediated currents, Dopamine
Current Topics in Medicinal Chemistry
Title: The NMDA/D1 Receptor Complex as a New Target in Drug Development
Volume: 6 Issue: 8
Author(s): Cristina Missale, Chiara Fiorentini, Chiara Busi, Ginetta Collo and P. F. Spano
Affiliation:
Keywords: glutamate transmission, cAMP-PKA pathway, bioluminescence resonance energy transfer (BRET), NMDA-mediated currents, Dopamine
Abstract: Dopamine and glutamate have been shown to extensively interact in the striatum, nucleus accumbens, hippocampus and prefrontal cortex, to regulate different physiological functions, including locomotor activity, positive reinforcement, attention and working memory. Although dysfunctions of dopamine transmission have long been identified as critical determinants of neurological and neuropsychiatric disorders, such as Parkinsons disease and schizophrenia, there is now increasing evidence that concurrent alterations of dopamine and glutamate function may play a central role in the pathophysiology of these diseases. Thus, defining the characteristics of dopamine-glutamate interactions may be crucial to identify alternative molecular targets for the development of novel pharmacological tools. At the postsynaptic level, interactions between the dopamine D1 and the glutamate NMDA receptors appear to be particularly relevant. Different mechanisms are involved in this interactions: 1) D1R-dependent, second messenger-mediated phosphorylation of NMDAR subunits; 2) coordinated regulation of receptor trafficking at synaptic sites; 3) formation of an heteromeric D1/NMDA receptor complex. In this paper we review the molecular mechanisms, functional implications and pharmacological significance of D1R/NMDAR interaction via direct protein-protein oligomerization.
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Cite this article as:
Missale Cristina, Fiorentini Chiara, Busi Chiara, Collo Ginetta and Spano F. P., The NMDA/D1 Receptor Complex as a New Target in Drug Development, Current Topics in Medicinal Chemistry 2006; 6 (8) . https://dx.doi.org/10.2174/156802606777057562
DOI https://dx.doi.org/10.2174/156802606777057562 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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