Last update 01 Nov 2024

NPY4R

Last update 01 Nov 2024

Basic Info

Synonyms

Neuropeptide Y receptor type 4, neuropeptide Y receptor Y4, NPY4-R

+ [5]

Introduction

G protein-coupled receptor for PPY/pancreatic polypeptide/PP, NPY/neuropeptide Y and PYY/peptide YY that is negatively coupled to cAMP (PubMed:7592911, PubMed:7493937). The rank order of affinity for these polypeptides and their derivatives is PP, PP (2-36) and [Ile-31, Gln-34] PP > [Pro-34] PYY > PYY and [Leu-31, Pro-34] NPY > NPY > PYY (3-36) and NPY (2-36) > PP (13-36) > PP (31-36) > NPY free acid.

Drugs associated with NPY4R

VU-0506013

Target

NPY4R

Mechanism

NPY4R modulators

Active Org.

Universität Leipzig

Originator Org.

Universität Leipzig

Active Indication

Obesity

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

BVD-74D

Target

NPY4R

Mechanism

NPY4R agonists

Active Org.

Monash University

Originator Org.

Monash University

Active Indication

Obesity

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

TM-30339

Target

NPY4R

Mechanism

NPY4R agonists

Active Org.-

Originator Org.

7TM Pharma

Active Indication-

Inactive Indication

Obesity

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with NPY4R

NCT00746824 / TerminatedPhase 2

TM30339: A Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel, Repeated Subcutaneous Dose-range Study Designed to Determine the Weight Loss in Obese Subjects.

The purpose of this study is to determine the effects of TM30339 on weight loss in obese individuals after 28 days dosing.

Start Date01 Aug 2008

Sponsor / Collaborator

7TM A/S

EUCTR2007-000993-22-SE / Not yet recruitingNot Applicable

A multi-centre, randomized, double-blind, placebo-controlled, parallel-group study in obese subjects investigating weight loss after repeated, subcutaneous doses of TM30338

Start Date02 May 2007

Sponsor / Collaborator

7TM A/S

100 Clinical Results associated with NPY4R

100 Translational Medicine associated with NPY4R

0 Patents (Medical) associated with NPY4R

288

Literatures (Medical) associated with NPY4R

01 Dec 2024·Computers in Biology and Medicine

Bioinformatic analysis of neuropeptide related genes in patients diagnosed with invasive breast carcinoma

Article

Author: Ayan, Durmus ; Yay, Fatih

PURPOSENeuropeptide receptors are expressed in many malignancies. Effectors involved in the action mechanisms of HCRTR1, HCRTR2, NPY4R (PPYR1) may be related to breast cancer (BC). Genes encoding these receptors and PPY and PTPN11 genes were aimed to examine via bioinformatics tools in the BRCA cohort. To our knowledge, this is the first study in which these receptor genes and PP, which have not found much research in BC, are examined together with PTPN11 and analyzed comprehensively in large patient cohorts from public databases.METHODScBioPortal was used for gene alteration analyses, GeneMania for association analyses with other genes, Kaplan-Meier Plotter for Overall Survival (OS) and Relapse Free Survival (RFS) analyses, UALCAN for methylation analyses, TIMER2.0 for expression analyses, The Human Protein Atlas database for expression validations, TIMER for immune infiltration analyses, WEKA 3.8.6 for diagnostic classification performances of the genes based on Random Forest Classifier and Enrichr-KG for Gene Ontology (GO) Biological Process (BP) and KEGG analysis.RESULTS19 (1.9 %) nucleotide changes were found in 996 cases. Missense mutation is most common. Decreased expression levels of the HCRTR1 gene were associated with shorter OS and RFS, but decreased expression levels of the PTPN11 gene were associated with longer OS and RFS. Decreased expression levels NPY4R (PPYR1) gene were associated with shorter RFS. Increased expression levels of HCRTR2 and PPY genes were associated with longer RFS. HCRTR1 and NPY4R (PPYR1) genes were statistically hypermethylated; conversely HCRTR2 and PPY genes were hypomethylated. There was no significant change in PTPN11 gene promoter methylation level. HCRTR1, NPY4R (PPYR1) and PTPN11 gene expressions were downregulated; conversely, HCRTR2 and PPY gene expressions upregulated. Weak correlations were observed between NPY4R (PPYR1) gene expression and CD4⁺ T Cell, Neutrophil, Dendritic Cell and between PTPN11 gene expression and CD8⁺ T Cell, Macrophage, Neutrophil, Dendritic Cell infiltrations. Area under the receiver operating characteristics curve values of the 10-fold cross-validation and by splitting the dataset in a ratio of 80:20 models were 0.930 and 0.963 respectively. HCRTR2 and HCRTR1 belong to regulation of cytosolic calcium ion concentration, cellular calcium ion homeostasis GO BPs.CONCLUSIONIn BC patients, increases in HCRTR2 and PPY gene expressions could be considered as positive prognostic factors. Decreases in HCRTR1 and NPY4R (PPYR1) gene expressions could be considered as negative prognostic factors. Decreased expression of PTPN11 gene may have a positive prognostic factor. Changes in existing genes are likely to be both a biomarker and therapeutic target for BC. However, experimental and clinical studies are needed to elucidate the mechanisms underlying these neuropeptide receptors in terms of breast carcinogenesis.

01 Oct 2024·Neuropeptides

Expression and localization of the neuropeptide Y-Y4 receptor in the chick spleen: mRNA upregulation by high ambient temperature

Article

Author: Gilbert, Elizabeth R ; Takahashi, Eiki ; Haraguchi, Shogo ; Chowdhury, Vishwajit S ; Cline, Mark A ; Itoh, Taichi Q ; Nishimura, Shotaro ; Bungo, Takashi ; Hosaka, Yoshinao Z ; Nishimura, Haruka ; Cockrem, John F ; Ouchi, Yoshimitsu ; Elhussiny, Mohamed Z

High ambient temperatures (HT) can increase diencephalic neuropeptide Y (NPY) expression, and central injection of NPY attenuates heat stress responses while inducing an antioxidative state in the chick spleen. However, there is a lack of knowledge about NPY receptor expression, and its regulation by HT, in the chick spleen. In the current study, male chicks were used to measure the expression of NPY receptors in the spleen and other immune organs under acute (30 vs. 40 ± 1°C for 3 h) or chronic (30 vs. 40 ± 1°C for 3 h/day for 3 days) exposure to HT and in response to central injection of NPY (47 pmol, 188 pmol, or 1 nmol). We found that NPY-Y4 receptor mRNA was expressed in the spleen, but not in other immune organs studied. Immunofluorescence staining revealed that NPY-Y4 receptors were localized in the splenic pulp. Furthermore, NPY-Y4 receptor mRNA increased in the chick spleen under both acute and chronic exposure to HT. Central NPY at two dose levels (47 and 188 pmol) and a higher dose (1 nmol) did not increase splenic NPY-Y4 receptor mRNA expression or splenic epinephrine under HT (35 ± 1°C), and significantly increased 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations under HT (40 ± 1°C). In conclusion, increased expression of NPY-Y4 receptor mRNA in the spleen under HT suggest that Y4 receptor may play physiological roles in response to HT in male chicks.

01 Jul 2024·Journal of Zhejiang University-SCIENCE B

Neuropeptide Y receptor Y8b (npy8br) regulates feeding and digestion in Japanese medaka (Oryzias latipes) larvae: evidence from gene knockout

Article

Author: Lu, Ke ; Liang, Xufang ; Jia, Xiaodan

Neuropeptide Y receptor Y8 (NPY8R) is a fish-specific receptor with two subtypes, NPY8AR and NPY8BR. Changes in expression levels during physiological processes or in vivo regulation after ventricular injection suggest that NPY8BR plays an important role in feeding regulation; this has been found in only a few fish, at present. In order to better understand the physiological function of npy8br, especially in digestion, we used clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology to generate npy8br^-/- Japanese medaka (Oryzias latipes). We found that the deletion of npy8br in medaka larvae affected their feeding and digestion ability, ultimately affecting their growth. Specifically, npy8br deficiency in medaka larvae resulted in decreased feed intake and decreased expression levels of orexigenic genes (npy and agrp). npy8br^-/- medaka larvae fed for 10 d (10th day of feeding) still had incompletely digested brine shrimp (Artemia nauplii) in the digestive tract 8 h after feeding, the messenger RNA (mRNA) expression levels of digestion-related genes (amy, lpl, ctra, and ctrb) were significantly decreased, and the activity of amylase, trypsin, and lipase also significantly decreased. The deletion of npy8br in medaka larvae inhibited the growth and significantly decreased the expression of growth-related genes (gh and igf1). Hematoxylin and eosin (H&E) sections of intestinal tissue showed that npy8br^-/- medaka larvae had damaged intestine, thinned intestinal wall, and shortened intestinal villi. So far, this is the first npy8br gene knockout model established in fish and the first demonstration that npy8br plays an important role in digestion.

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