Last update 01 Nov 2024

NTSR2

Last update 01 Nov 2024

Basic Info

Synonyms

Levocabastine-sensitive neurotensin receptor, neurotensin receptor 2, Neurotensin receptor type 2

+ [3]

Introduction

Receptor for the tridecapeptide neurotensin. It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system.

Drugs associated with NTSR2

NTRC-808

Target

NTSR2

Mechanism

NTSR2 agonists

Active Org.

Research Triangle Institute

Originator Org.

Research Triangle Institute

Active Indication

Nervous System Diseases

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

NTRC-739

Target

NTSR2

Mechanism

NTSR2 modulators

Active Org.

Research Triangle Institute

Originator Org.

Research Triangle Institute

Active Indication

Pain

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

NTRC-824

Target

NTSR2

Mechanism

NTSR2 antagonists

Active Org.

Research Triangle Institute

Originator Org.

Research Triangle Institute

Active Indication

Pain

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with NTSR2

100 Translational Medicine associated with NTSR2

0 Patents (Medical) associated with NTSR2

318

Literatures (Medical) associated with NTSR2

19 Sep 2024·Pain

The conotoxin Contulakin-G reverses hypersensitivity observed in rodent models of cancer-induced bone pain without inducing tolerance or motor disturbance.

Article

Author: Moutal, Aubin ; Ismail, Khaled A ; Cheng, Kevin ; Khanna, Rajesh ; Olivera, Baldomero M ; Price, Theodore J ; Vanderah, Todd W ; Patwardhan, Amol ; Martin, Laurent F ; Stratton, Harrison J ; Ibrahim, Mohab M ; Almuslim, Moyad

ABSTRACTAs the incidence and survival rates of patients with cancer continues to grow, an increasing number of people are living with comorbidities, which often manifests as cancer-induced bone pain (CIBP). The majority of patients with CIBP report poor pain control from currently available analgesics. A conotoxin, Contulakin-G (CGX), has been demonstrated to be an antinociceptive agent in postsurgical and neuropathic pain states via a neurotensin receptor 2 (NTSR2)-mediated pathway. However, the efficacy and side effect profile of CGX have never been assessed in CIBP. Here, we evaluated CGX's antinociceptive potential in a rodent model of CIBP. We hypothesized that CGX engages the NTSR2 pathway, providing pain relief with minimal tolerance and motor side effects. Our results demonstrated that CGX intrathecal injection in mice with CIBP attenuated both spontaneous pain behaviors and evoked mechanical hypersensitivity, regardless of their sex. Furthermore, the antinociceptive effect of CGX was dependent upon expression of NTSR2 and the R-type voltage-gated calcium channel (Cav2.3); gene editing of these targets abolished CGX antinociception without affecting morphine antinociception. Examination of the side effect profile of CGX demonstrated that, unlike morphine, chronic intrathecal infusion maintained antinociception with reduced tolerance in rats with CIBP. Moreover, at antinociceptive doses, CGX had no impact on motor behavior in rodents with CIBP. Finally, RNAScope and immunoblotting analysis revealed expression of NTSR2 in both dorsal and ventral horns, while Cav2.3 was minimally expressed in the ventral horn, possibly explaining the sensory selectivity of CGX. Together, these findings support advancing CGX as a potential therapeutic for cancer pain.

31 Aug 2024·The FASEB Journal

Interferon‐gamma signaling drives epithelial TNF‐alpha receptor‐2 expression during colonic tissue repair

Article

Author: Parkos, Charles A. ; Nusrat, Asma ; Quiros, Miguel ; Watson, Sean ; Cabrera‐Silva, Rodolfo I.

AbstractInterferon‐gamma (IFNγ) is traditionally recognized for its pro‐inflammatory role during intestinal inflammation. Here, we demonstrate that IFNγ also functions as a pro‐repair molecule by increasing TNFα receptor 2 (TNFR2 protein/TNFRSF1B gene) expression on intestinal epithelial cells (IEC) following injury in vitro and in vivo. In silico analyses identified binding sites for the IFNγ signaling transcription factor STAT1 in the promoter region of TNFRSF1B. Scratch‐wounded IEC exposed to IFNγ exhibited a STAT1‐dependent increase in TNFR2 expression. In situ hybridization revealed elevated Tnfrsf1b mRNA levels in biopsy‐induced colonic mucosal wounds, while intraperitoneal administration of IFNγ neutralizing antibodies following mucosal injury resulted in impaired IEC Tnfrsf1b mRNA and inhibited colonic mucosal repair. These findings challenge conventional notions that “pro‐inflammatory” mediators solely exacerbate damage by highlighting latent pro‐repair functions. Moreover, these results emphasize the critical importance of timing and amount in the synthesis and release of IFNγ and TNFα during the inflammatory process, as they are pivotal in restoring tissue homeostasis.

01 May 2024·Current Neuropharmacology

Neurotensin and Neurotensin Receptors in Stress-related Disorders: Pathophysiology & Novel Drug Targets

Review

Author: Kyriatzis, Grigorios ; Khrestchatisky, Michel ; Chatzaki, Ekaterini Alexiou ; Ferhat, Lotfi

Abstract:Neurotensin (NT) is a 13-amino acid neuropeptide widely distributed in the CNS that has been involved in the pathophysiology of many neural and psychiatric disorders. There are three known neurotensin receptors (NTSRs), which mediate multiple actions, and form the neurotensinergic system in conjunction with NT. NTSR1 is the main mediator of NT, displaying effects in both the CNS and the periphery, while NTSR2 is mainly expressed in the brain and NTSR3 has a broader expression pattern. In this review, we bring together up-to-date studies showing an involvement of the neurotensinergic system in different aspects of the stress response and the main stress-related disorders, such as depression and anxiety, post-traumatic stress disorder (PTSD) and its associated symptoms, such as fear memory and maternal separation, ethanol addiction, and substance abuse. Emphasis is put on gene, mRNA, and protein alterations of NT and NTSRs, as well as behavioral and pharmacological studies, leading to evidence-based suggestions on the implicated regulating mechanisms as well as their therapeutic exploitation. Stress responses and anxiety involve mainly NTSR1, but also NTSR2 and NTSR3. NTSR1 and NTSR3 are primarily implicated in depression, while NTSR2 and secondarily NTSR1 in PTSD. NTSR1 is interrelated with substance and drug abuse and NTSR2 with fear memory, while all NTSRs seem to be implicated in ethanol consumption. Some of the actions of NT and NTSRs in these pathological settings may be driven through interactions between NT and corticotrophin releasing factor (CRF) in their regulatory contribution, as well as by NT’s pro-inflammatory mediating actions.

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NTSR2

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