Neurotensin NTS1-dopamine D2 receptor-receptor interactions in putative receptor heteromers: relevance for Parkinson's disease and schizophrenia.

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