Multitasking with neurotensin in the central nervous system

Abstract

The 13-amino acid peptide neurotensin (NT) was discovered over 30 years ago and has been implicated in a wide variety of neurotransmitter and endocrine functions. This review focuses on four areas where there has been substantial recent progress in understanding NT signaling and several functions of the endogenous peptide. The first area concerns the functional activation of the high-affinity NT receptor, NTR-1, including the delineation of the NT binding pocket and receptor domains involved in functional coupling to intracellular signaling pathways. The development of NT receptor antagonists and the application of genetic and molecular genetic approaches have accelerated progress in understanding NT function in several areas, including the involvement of NT in antipsychotic drug actions, psychostimulant sensitization and the modulation of pain, and these are reviewed in that order. There is now substantial evidence indicating that NT is required for certain antipsychotic drug actions and that the peptide plays a key role in stress-induced analgesia.

Endogenous CNS Expression of Neurotensin and Neurotensin Receptors Is Altered during the Postpartum Period in Outbred Mice

“…NT and its receptors are found in a number of brain regions linked to maternal behavior, including the nucleus accumbens (NAcc), lateral septum (LS), bed nucleus of the stria terminalis, dorsal (BnSTd), MPOA, paraventricular nucleus (PVN), lateral hypothalamus (LH), central and basolateral amygdala (BLA/CeA), and ventral tegmental area (VTA) [22]–[28]. NT signaling is often linked to dopamine signaling in various regions [29], [30], and dopamine itself has been linked to maternal care [31]–[33]. In addition to modulating the activity of the hypothalamic pituitary adrenal (HPA) axis [34], [35], NT release and activation of NT receptors have been shown to affect temperature regulation [36], [37] and pain perception [38].…”

Neurotensin inversely modulates maternal aggression

“…NT acts most commonly via either NT receptor 1 (NT1) or receptor 2 (NT2) (Tanaka et al, 1990, Richard et al, 2001, Sarret et al, 2002), but it can also act via NT receptor 3, a sortilin receptor that internalizes the ligand (Mazella, 2001). NT and its receptors are highly conserved among mammals (Dobner, 2005). Although NT is expressed in and acts upon a number of areas critical for social behavior, including nucleus accumbens, lateral septum (LS), bed nucleus of stria terminalis (BNST), preoptic area, amygdala, and periaqueductal gray (Boudin et al, 1996, Binder et al, 2001a, Sarret et al, 2003), it has received almost no research attention regarding its role in social behaviors.…”

Intermolecular interactions between the neurotensin and the third extracellular loop of human neurotensin 1 receptor

“…Both NTS1 and NTS2 are G-protein-coupled receptors (GPCRs) with seven putative transmembrane domains (TMs) connected by an extracellular and intracellular loops, an extracellular N-terminus, and an intracellular C-terminus. Most of the known biological and physiological effects are mediated through the NTS1 receptor (Dobner, 2005;Dubuc et al, 1999;Gully et al, 1993;Pettibone et al, 2002).…”