title: Increased Brain Neurotensin and NTSR2 Lead to Weak Nociception in NTSR3/Sortilin Knockout Mice.
abstract: The neuropeptide neurotensin (NT) elicits numerous pharmacological effects through three different receptors (NTSR1, NTSR2, and NTSR3 also called sortilin). Pharmacological approaches and generation of NTSR1 and NTSR2-deficient mice allowed to determine the NT-induced antipsychotic like behavior, the inhibitory of weak fear memory and the nociceptive signaling in a rat formalin tonic pain model to NTSR1. Conversely, the effects of NT on thermal and tonic nociceptions were mediated by NTSR2. However, the role of NTSR3/sortilin on the neurotensinergic system was not investigated. Here, by using C57Bl/6J mouse model in which the gene coding for NTSR3/sortilin has been inactivated, we observed a modification of the expression of both NTSR2 and NT itself. Quantitative PCR and protein expression using Western blot analyses and AlphaLisa™ technology resulted in the observation that brain NTSR2 as well as brain and blood NT were 2-fold increased in KO mice leading to a resistance of these mice to thermal and chemical pain. These data confirm that NTSR3/sortilin interacts with other NT receptors (i.e., NTSR2) and that its deletion modifies also the affinity of this receptor to NT.
authors.affiliation: CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275, Université de Nice Sophia Antipolis Valbonne, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Devader
authors.affiliation: CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275, Université de Nice Sophia Antipolis Valbonne, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Moreno
authors.affiliation: CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275, Université de Nice Sophia Antipolis Valbonne, France.
authors.forename: Morgane
authors.initials: M
authors.lastname: Roulot
authors.affiliation: CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275, Université de Nice Sophia Antipolis Valbonne, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Deval
authors.affiliation: Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, Medical University of South CarolinaCharleston, SC, USA; JT Pharmaceuticals, Inc.Mount Pleasant, SC, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dix
authors.affiliation: Department of Anatomy and Cell Biology, McGill University Montreal, QC, Canada.
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Morales
authors.affiliation: CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275, Université de Nice Sophia Antipolis Valbonne, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Mazella
keywords: knockout gene; neurotensin; nociception; receptor; sortilin