Neurotensin GPCR Assays
Background of Neurotensin Receptors
First detected in 1973, neurotensin is a 13-1mino acid regulatory peptide present in both the central nervous system and the gastrointestinal tract. Neurotensin receptors are transmembrane receptors that bind the neurotransmitter neurotensin for multiple physiological functions. In various cancers, neurotensin and its receptors can promote cell proliferation, DNA synthesis, migration, and angiogenesis through autocrine and paracrine effects.
Fig.1 Summary of the role of NT/NTSR1 in non-gastrointestinal cancers. (Nikolaou, 2020)
Distribution and Functions of Neurotensin Receptors
The high-affinity NTSR1 (neurotensin receptor 1) is distributed widely throughout the brain and gastrointestinal tract to mediate the GI functions of neurotensin. The expression of NTSR2 can be detected in the brain which involves the descending control of nociception and other extragastrointestinal sites.
Subtypes and Mechanisms of Neurotensin Receptors
There are three types of neurotensin receptors that bind the neurotransmitter neurotensin, including the G-protein-coupled receptors NTS1 and NTS2, as well as the single transmembrane receptor NTS3.
| Receptor | Gene | Mechanism | Agonists | Antagonists |
| Neurotensin receptor 1 | NTSR1 |
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| Neurotensin receptor 2 | NTSR2 |
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Assay List of Neurotensin Receptors
Creative Biolabs can provide a range of assays of neurotensin receptors. You can choose the assay in the list or contact us for more information:
Published Data
| Paper Title | Structure of the neurotensin receptor 1 in complex with β-arrestin 1 |
| Journal | Nature |
| Published | 2020 |
| Abstract | The binding of Arrestin proteins to active phosphorylated G protein-coupled receptors (GPCRs) can prevent G protein coupling and trigger receptor internalization and ultimately affect various downstream signaling pathways. Over the past few decades, structural information on the interaction between GPCRs and G proteins has become available. Phosphorylation of NTSR1 is critical for forming a stable complex with βarr1 (ΔCT). In this paper, we report the structure of full-length human NTSR1 in complex with truncated human β-arrestin 1 (βarr1(ΔCT)). Furthermore, we found that a bridge is formed between the phosphatidylinositol-4,5-bisphosphate molecule and the C lobe of arrestin. These findings highlight conserved aspects and plasticity of arrestin-receptor interactions. |
| Result |
NTSR1 mediates responses to neurotensin (NTS) and neuromedin N. NTS can regulate a variety of physiological processes, including blood pressure, ileal contraction, analgesia, or hypothermia. There is already evidence that most of the physiological responses to NTS are mediated by NTSR1. Both the active and inactive state structures of NTSR1 have been crystallographically determined. In addition, the structure of the NTSR1-Gi complex has also been determined. The NTSR1-Gi1 complex was found to have two distinct conformations, termed the C state (canonical state) and the NC state (noncanonical state). Recent studies have shown that an arrestin-biased positive allosteric modulator of NTSR1 inhibits methamphetamine self-administration in rats, providing further impetus for elucidating the structure of the NTSR1-βarr1 complex.
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Fig.2 Phosphorylation of NTSR1 is crucial for βarr1 coupling. (Huang, 2020)
References
- Nikolaou, S.; et al. The role of Neurotensin and its receptors in non-gastrointestinal cancers: a review. Cell Communication and Signaling. 2020, 18(1): 1-10.
- Huang, W.; et al. Structure of the neurotensin receptor 1 in complex with β-arrestin 1. Nature. 2020, 579(7798): 303-308.
