Last update 01 Nov 2024

NPY5R

Last update 01 Nov 2024

Basic Info

Synonyms

Neuropeptide Y receptor type 5, neuropeptide Y receptor Y5, NPY-Y5 receptor

+ [5]

Introduction

Receptor for neuropeptide Y and peptide YY. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity. Seems to be associated with food intake. Could be involved in feeding disorders.

Drugs associated with NPY5R

FR233118

Target

NPY5R

Mechanism

NPY5R antagonists

Active Org.

Fujisawa Pharmaceutical Co., Ltd.

Originator Org.

Fujisawa Pharmaceutical Co., Ltd.

Active Indication

Obesity

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

SCH 488106

Target

NPY5R

Mechanism

NPY5R antagonists

Active Org.

Schering-Plough Research Institute

Originator Org.

Schering-Plough Research Institute

Active Indication

Obesity

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

SCH 208639

Target

NPY5R

Mechanism

NPY5R antagonists

Active Org.

Schering-Plough Research Institute

Originator Org.

Schering-Plough Research Institute

Active Indication

Obesity

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with NPY5R

JPRN-jRCT2080222949 / Unknown statusPhase 2

A Phase 2 study of S-237648 in Japanese obese patients with impaired glucose tolerance/type 2 diabetes mellitus and hyperlipidemia

Start Date31 Aug 2015

Sponsor / Collaborator

Shionogi & Co., Ltd.

JPRN-jRCT2080221761 / Unknown statusPhase 2

Phase 2b, Double-Blind, Parallel-group Study of S-2367 in Obese Patients

Start Date06 Apr 2012

Sponsor / Collaborator

Shionogi & Co., Ltd.

JPRN-JapicCTI-121803 / Unknown statusPhase 2

Phase 2b, Double-Blind, Parallel-group Study of S-2367 in Obese Patients

Start Date01 Mar 2012

Sponsor / Collaborator

Shionogi & Co., Ltd.

100 Clinical Results associated with NPY5R

100 Translational Medicine associated with NPY5R

0 Patents (Medical) associated with NPY5R

398

Literatures (Medical) associated with NPY5R

01 Dec 2024·Molecular and Cellular Endocrinology

The adipose tissue melanocortin 3 receptor is targeted by ghrelin and leptin and may be a therapeutic target in obesity

Article

Author: Rosendo-Silva, Daniela ; Abrantes, Ana Margarida ; Eickhoff, Hans ; Seiça, Raquel ; Botelho, Maria Filomena ; Lopes, Eduardo ; Viana, Sofia ; Reis, Flávio ; Monteiro-Alfredo, Tamaeh ; Falcão-Pires, Inês ; Pires, Ana Salomé ; Matafome, Paulo

OBJECTIVEObesity is linked to perturbations in energy balance mechanisms, including ghrelin and leptin actions at the hypothalamic circuitry of neuropeptide Y (NPY) and melanocortin. However, information about the regulation of this system in the periphery is still scarce. Our objective was to study the regulation of the NPY/melanocortin system in the adipose tissue (AT) and evaluate its therapeutic potential for obesity and type 2 diabetes.METHODSThe expression of the NPY/melanocortin receptors' levels was assessed in the visceral AT of individuals with obesity and altered metabolism. Protein levels of these receptors were evaluated in cultured adipocytes incubated with ghrelin (30 and 100 ng/mL) and leptin (1 and 10 nM) and in the AT of an animal model with a mutation in the leptin receptor (ZSF1 rat), to understand their regulation by leptin and ghrelin. The vertical sleeve gastrectomy animal model was used to evaluate the putative therapeutic potential of the NPY/melanocortin system.RESULTSIn this study, we unravelled that leptin (1 nM and 10 nM) selectively reduced the levels of NPY5R and MC3R but no other NPYR/MCRs in cultured adipocytes. In turn, acylated ghrelin (100 ng/mL) significantly increased NPY1R, but the inhibition of its receptor also abrogates MC3R levels. However, in the Lepr-deficient ZSF1 rat, both NPY5R and MC3R levels were reduced, along with other NPYRs and MCRs, suggesting that leptin resistance negatively affects NPY and melanocortin signalling. In human adipose tissue, we found a downregulation of genes encoding the NPY and melanocortin receptors in the visceral AT of individuals with obesity and insulin resistance, being correlated with genes regulating metabolic activity. Additionally, diabetic obese rats submitted to vertical sleeve gastrectomy showed increased levels of NPY, melanocortin, ghrelin, and leptin receptors in the AT, including MC3R, suggesting it may constitute a therapeutic target in obesity.CONCLUSIONSOur results suggest that the AT NPY/melanocortin system, particularly the MC3R, may be involved in the neuroendocrine regulation of adipocyte metabolism. Altogether, our work shows MC3R is under the control of the ghrelin/leptin duo, is reduced in patients with obesity and prediabetes, and may constitute a therapeutic target in obesity.

21 Aug 2024·The Journal of Neuroscience

Activation of NPY Receptors in the BLA Inhibits Projections to the Bed Nucleus of the Stria Terminalis and Buffers Stress-Induced Decreases in Social Interaction in Male Rats

Article

Author: Vantrease, Jaime E ; Bompolaki, Maria ; DeJoseph, M Regina ; Miranda Tapia, Ana P ; Colmers, William F ; Urban, Janice H

Neuropeptide Y (NPY) increases resilience and buffers behavioral stress responses in male rats in part through decreasing the excitability of principal output neurons in the basolateral amygdala (BLA). Intra-BLA administration of NPY acutely increases social interaction (SI) through activation of either Y1or Y5receptors, whereas repeated NPY (rpNPY) injections (once daily for 5 d) produce persistent increases in SI through Y5receptor-mediated neuroplasticity in the BLA. In this series of studies, we characterized the neural circuits from the BLA that underlie these behavioral responses to NPY. Using neuronal tract tracing, NPY Y1and Y5receptor immunoreactivity was identified on subpopulations of BLA neurons projecting to the bed nucleus of the stria terminalis (BNST) and the central nucleus of the amygdala (CeA). Inhibition of BLA→BNST, but not BLA→CeA, neurons using projection-restricted, cre-driven designer receptors exclusively activated by designer drug-Giexpression increased SI and prevented stress-induced decreases in SI produced by a 30 min restraint stress. This behavioral profile was similar to that seen after both acute and rpNPY injections into the BLA. Intracellular recordings of BLA→BNST neurons demonstrated NPY-mediated inhibition via suppression of H currents, as seen previously. Repeated intra-BLA injections of NPY, which are associated with the induction of BLA neuroplasticity, decreased the activity of BLA→BNST neurons and decreased their dendritic complexity. These results demonstrate that NPY modulates the activity of BNST-projecting BLA neurons, suggesting that this pathway contributes to the stress-buffering actions of NPY and provides a novel substrate for the proresilient effects of NPY.

01 Jun 2024·ESC Heart Failure

Subarachnoid haemorrhage‐induced reversible cardiac dysfunction: time course and potential mechanisms

Article

Author: Xiao, Yichao ; Wang, Zhuo ; Liu, Qiming ; Chen, Mingxian ; Wu, Zhihong ; Zhou, Shenghua ; Lai, Xin ; Wang, Songyun

AbstractAimsCardiac dysfunction is commonly observed in patients with subarachnoid haemorrhage (SAH). However, the specific timeline of cardiac remodelling and the underlying mechanisms responsible for this effect following SAH remain unknown. This study aims to explore the impact of SAH on cardiac dysfunction and its potential mechanisms over time.Methods and resultsIn Protocol 1, we investigated cardiac function and potential mechanisms in a Sprague‐Dawley rat model of SAH at six time points (baseline and Days 1, 3, 7, 14, and 28) while exploring the underlying mechanisms. Our assessments included the haemodynamic profile, echocardiography, and the concentrations of plasma biomarkers at various time points post‐SAH. We determined neuropeptide Y (NPY) 1–5 receptor protein expression levels through western blotting. In Protocol 2, we administered an NPY1 receptor antagonist to evaluate the effects of cardiac dysfunction induced by SAH on Day 3. In Protocol 1, SAH gradually provoked cardiac systolic dysfunction during the acute phase, reaching its peak on Day 3 without concurrent alterations in wall thickness. However, no significant changes were observed from Days 14 to 28 compared with Day 0. The changes in cardiac dysfunction were consistent with myocardial injury, inflammatory biomarkers, and NPY levels. SAH resulted in a heightened heart rate and systolic blood pressure, correlating with elevated epinephrine and norepinephrine levels. In Protocol 2, the administration of the NPY1 receptor antagonist effectively ameliorated cardiac dysfunction.ConclusionsSAH induces transient cardiac dysfunction in the acute phase, and the underlying mechanisms for this response involve the NPY–NPY1 receptor pathway, otherwise known as catecholamines.

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NPY5R

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