Background & Aims: The neuropeptide neurotensin (NT) exerts its intracellular effect by interacting with 3 different receptors. Two of these receptors (NTR1 and NTR2) belong to the G protein-coupled receptor family, whereas the third one (NTR3) is a type I receptor with a single transmembrane domain. We recently showed that the 2 structurally different receptors NTR1 and NTR3 were coexpressed in several human cancer cells on which NT exerts proliferative effects.
Methods: Here, by an immunoprecipitation approach, we provide biochemical evidence for an endogenous heterodimerization of the G protein-coupled receptor NTR1 with the NTR3 in the human adenocarcinoma cell line HT29.
Results: We show that both receptors are expressed and colocalized within the cell surface of HT29 cells where they already interact to form a heterodimer. The NTR1-NTR3 complex is then internalized on NT stimulation.
Conclusions: The complex formed between these 2 structurally unrelated NT receptors modulates both the NT-induced phosphorylation of mitogen-activated protein kinases and the phosphoinositide (PI) turnover mediated by the NTR1.
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http://dx.doi.org/10.1053/gast.2002.36000 | DOI Listing |
ACS Chem Biol
January 2025
Department Chemistry and Biochemistry Clemens-Schöpf-Institute, Technical University Darmstadt, Peter-Grünberg Straße 4, Darmstadt 64287, Germany.
Class A G protein-coupled receptors (GPCRs) are key mediators in numerous signaling pathways and important drug targets for several diseases. A major shortcoming in GPCR ligand screening is the detection limit for weak binding molecules, which is especially critical for poorly druggable GPCRs. Here, we present a proximity-based screening system for class A GPCRs, which adopts the natural two-step activation mechanism of class B GPCRs.
View Article and Find Full Text PDFInt J Mol Sci
October 2024
Department of Fertility Medicine, CHRU de Nancy, Université de Lorraine, F-54000 Nancy, France.
Neurotensin (NT) is a peptide involved in digestion, neuromodulation, and cancer progression. NT and its receptors (NTR1 and SORT1 mainly) have been widely studied in oncology. Data show that NT expression is under the control of sex steroid hormones, in particular estradiol.
View Article and Find Full Text PDFNeurogastroenterol Motil
December 2024
Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
Background: An impaired intestinal barrier with the activation of corticotropin-releasing factor (CRF), Toll-like receptor 4 (TLR4), and proinflammatory cytokine signaling, resulting in visceral hypersensitivity, is a crucial aspect of irritable bowel syndrome (IBS). The gut exhibits abundant expression of neurotensin; however, its role in the pathophysiology of IBS remains uncertain. This study aimed to clarify the effects of PD149163, a specific agonist for neurotensin receptor 1 (NTR1), on visceral sensation and gut barrier in rat IBS models.
View Article and Find Full Text PDFEJNMMI Res
June 2024
Department of Nuclear Medicine, Xiangya Hospital, Central South University, No.87 Xiangya Road, Changsha City, 410008, Hunan Province, P.R. China.
Background: Studies on single-target PET imaging of gastrin-releasing peptide receptor (GRPR), prostate-specific membrane antigen (PSMA), or neurotensin receptor 1(NTR1) have been reported. However, the performance of these three targets in the progression of PCa remains unclear. Our study aims to compare the expression of GRPR, PSMA, and NTR1 in patients with prostatic intraepithelial neoplasia (PIN), prostate cancer (PCa), and lymph node metastasis.
View Article and Find Full Text PDFGene
February 2024
College of Forestry and Biotechnology, Zhejiang A & F University, Hangzhou 311300, China. Electronic address:
The pine-wood invasive species nematode Bursaphelenchus xylophilus causes great forestry damage globally, particularly in Eurasia. B. xylophilus can hybridize with its native sibling, Bursaphelenchus mucronatus, with whom it shares an interestingly asymmetric mating behavior.
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