In the mammalian brain, the tridecapeptide neurotensin acts as a primary neurotransmitter or neuromodulator of classical neurotransmitters and numerous studies suggest the existence of a functional neurotensin/dopamine interaction. Among others, a possible molecular mechanism underlying the neurotensin-induced modulation of dopamine release is a direct antagonistic interaction between the NT receptor subtype 1 (NTS1) and the dopamine D2 receptor, including the D2 autoreceptor. More recently, biochemical, neurochemical and coimmunoprecipitation experiments also supported the existence of a NTS1/D2 receptor heteromer. The present mini-review attempts to provide a summary of current knowledge, mainly emerging from our microdialysis studies, supporting the existence 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.
Neurotensin NTS1-dopamine D2 receptor-receptor interactions in putative receptor heteromers: relevance for Parkinson's disease and schizophrenia.
FERRARO, Luca Nicola;RAVANI, Annalisa;TOMASINI, Maria Cristina;BORELLI, Andrea Celeste;ANTONELLI, Tiziana;TANGANELLI, Sergio;
2014
Abstract
In the mammalian brain, the tridecapeptide neurotensin acts as a primary neurotransmitter or neuromodulator of classical neurotransmitters and numerous studies suggest the existence of a functional neurotensin/dopamine interaction. Among others, a possible molecular mechanism underlying the neurotensin-induced modulation of dopamine release is a direct antagonistic interaction between the NT receptor subtype 1 (NTS1) and the dopamine D2 receptor, including the D2 autoreceptor. More recently, biochemical, neurochemical and coimmunoprecipitation experiments also supported the existence of a NTS1/D2 receptor heteromer. The present mini-review attempts to provide a summary of current knowledge, mainly emerging from our microdialysis studies, supporting the existence 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.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.