title: Neurotensin NTS1-dopamine D2 receptor-receptor interactions in putative receptor heteromers: relevance for Parkinson's disease and 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.
authors.forename: Luca
authors.initials: L
authors.lastname: Ferraro
authors.forename: Sarah
authors.initials: S
authors.lastname: Beggiato
authors.forename: Dasiel O
authors.initials: DO
authors.lastname: Borroto-Escuela
authors.forename: Laura
authors.initials: L
authors.lastname: Ravani
authors.forename: William T
authors.initials: WT
authors.lastname: O'Connor
authors.forename: Maria C
authors.initials: MC
authors.lastname: Tomasini
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Borelli
authors.forename: Luigi F
authors.initials: LF
authors.lastname: Agnati
authors.forename: Tiziana
authors.initials: T
authors.lastname: Antonelli
authors.forename: Sergio
authors.initials: S
authors.lastname: Tanganelli
authors.affiliation: Department of Life Sciences and Biotechnology, Section of Medicinal and Health Products, University of Ferrara, Via Fossato di Mortara 17-19, 44100 Ferrara, Italy. frl@unife.it.
authors.forename: Kjell
authors.initials: K
authors.lastname: Fuxe
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D009496:Neurotensin / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D018028:Receptors, Neurotensin / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism*; D009435:Synaptic Transmission; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D017448:Receptors, Dopamine D2; D018028:Receptors, Neurotensin; C114036:neurotensin type 1 receptor; D009496:Neurotensin; D005680:gamma-Aminobutyric Acid; D004298:Dopamine