Abstract
The tridecapeptide neurotensin (NT) acts as neurotransmitter in the central nervous system and in the periphery. NT and NT receptors are largely localized in dopamine (DA)-enriched regions of the mammalian brain. Accordingly, numerous studies indicate the presence of close functional interactions between DA neurons and the peptide. Among others mechanisms, it has been suggested that NT could modulate nigrostriatal, mesolimbic and meso-cortical DA transmission through an antagonistic receptor-receptor interaction between the NT receptor subtype 1 (NTS1) and the dopamine D2 receptor (D2R). In particular, it was originally demonstrated that the peptide reduces the D2R agonist affinity in striatal sections and in striatal membrane preparations. These effects could be a consequence of the direct allosteric NTS1/D2 receptor interactions leading to a decrease in the DA agonist affinity at the D2 receptor. Several neurochemical, biochemical and co-immunoprecipitation data have successively reinforced the indication of the presence of direct NTS1-D2 receptor interactions in the mammalian brain. The present mini-review attempts to provide a summary of current knowledge, mainly emerging from our microdialysis studies, supporting the presence of a NTS1/D2 receptor heteromer in the brain. The pre and post-synaptic mechanisms underlying the involvement of this heteromer in the striatopallidal GABA and mesocorticolimbic DA neurotransmission are discussed especially for their relevance in Parkinson’s disease and schizophrenia, respectively.
Keywords: Basal ganglia, GABA, glutamate, mesocorticolimbic dopaminergic pathway, microdialysis, neurotensin receptor, Parkinson’s disease, schizophrenia.
Current Protein & Peptide Science
Title:Neurotensin NTS1-Dopamine D2 Receptor-Receptor Interactions in Putative Receptor Heteromers: Relevance for Parkinson`s Disease and Schizophrenia
Volume: 15 Issue: 7
Author(s): Luca Ferraro, Sarah Beggiato, Dasiel O. Borroto-Escuela, Laura Ravani, William T. O'Connor, Maria C. Tomasini, Andrea C. Borelli, Luigi F. Agnati, Tiziana Antonelli, Sergio Tanganelli and Kjell Fuxe
Affiliation:
Keywords: Basal ganglia, GABA, glutamate, mesocorticolimbic dopaminergic pathway, microdialysis, neurotensin receptor, Parkinson’s disease, schizophrenia.
Abstract: The tridecapeptide neurotensin (NT) acts as neurotransmitter in the central nervous system and in the periphery. NT and NT receptors are largely localized in dopamine (DA)-enriched regions of the mammalian brain. Accordingly, numerous studies indicate the presence of close functional interactions between DA neurons and the peptide. Among others mechanisms, it has been suggested that NT could modulate nigrostriatal, mesolimbic and meso-cortical DA transmission through an antagonistic receptor-receptor interaction between the NT receptor subtype 1 (NTS1) and the dopamine D2 receptor (D2R). In particular, it was originally demonstrated that the peptide reduces the D2R agonist affinity in striatal sections and in striatal membrane preparations. These effects could be a consequence of the direct allosteric NTS1/D2 receptor interactions leading to a decrease in the DA agonist affinity at the D2 receptor. Several neurochemical, biochemical and co-immunoprecipitation data have successively reinforced the indication of the presence of direct NTS1-D2 receptor interactions in the mammalian brain. The present mini-review attempts to provide a summary of current knowledge, mainly emerging from our microdialysis studies, supporting the presence of a NTS1/D2 receptor heteromer in the brain. The pre and post-synaptic mechanisms underlying the involvement of this heteromer in the striatopallidal GABA and mesocorticolimbic DA neurotransmission are discussed especially for their relevance in Parkinson’s disease and schizophrenia, respectively.
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Ferraro Luca, Beggiato Sarah, Borroto-Escuela O. Dasiel, Ravani Laura, O'Connor T. William, Tomasini C. Maria, Borelli C. Andrea, Agnati F. Luigi, Antonelli Tiziana, Tanganelli Sergio and Fuxe Kjell, Neurotensin NTS1-Dopamine D2 Receptor-Receptor Interactions in Putative Receptor Heteromers: Relevance for Parkinson`s Disease and Schizophrenia, Current Protein & Peptide Science 2014; 15 (7) . https://dx.doi.org/10.2174/1389203715666140901105253
DOI https://dx.doi.org/10.2174/1389203715666140901105253 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
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