TY - JOUR
T1 - Neurotensin NTS1-dopamine D2 receptor-receptor interactions in putative receptor heteromers
T2 - Relevance for Parkinson’s disease and Schizophrenia
AU - Ferraro, Luca
AU - Beggiato, Sarah
AU - Borroto-Escuela, Dasiel O.
AU - Ravani, Laura
AU - O’Connor, William T.
AU - Tomasini, Maria C.
AU - Borelli, Andrea C.
AU - Agnati, Luigi F.
AU - Antonelli, Tiziana
AU - Tanganelli, Sergio
AU - Fuxe, Kjell
N1 - Publisher Copyright:
© 2014 Bentham Science Publishers.
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
AB - 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.
KW - Basal ganglia
KW - GABA
KW - Glutamate
KW - Mesocorticolimbic dopaminergic pathway
KW - Microdialysis
KW - Neurotensin receptor
KW - Parkinson’s disease
KW - Schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=84930164857&partnerID=8YFLogxK
U2 - 10.2174/1389203715666140901105253
DO - 10.2174/1389203715666140901105253
M3 - Article
C2 - 25175457
AN - SCOPUS:84930164857
SN - 1389-2037
VL - 15
SP - 681
EP - 690
JO - Current Protein and Peptide Science
JF - Current Protein and Peptide Science
IS - 7
ER -