Citations to this article

Food intake in free-feeding and energy-deprived lean rats is mediated by the neuropeptide Y5 receptor.
L Criscione, … , K G Hofbauer, N Levens
L Criscione, … , K G Hofbauer, N Levens
Published December 15, 1998
Citation Information: J Clin Invest. 1998;102(12):2136-2145. https://doi.org/10.1172/JCI4188.
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Research Article

Food intake in free-feeding and energy-deprived lean rats is mediated by the neuropeptide Y5 receptor.

Abstract

The new neuropeptide Y (NPY) Y5 receptor antagonist CGP 71683A displayed high affinity for the cloned rat NPY Y5 subtype, but > 1, 000-fold lower affinity for the cloned rat NPY Y1, Y2, and Y4 subtypes. In LMTK cells transfected with the human NPY Y5 receptor, CGP 71683A was without intrinsic activity and antagonized NPY-induced Ca2+ transients. CGP 71683A was given intraperitoneally (dose range 1-100 mg/kg) to a series of animal models of high hypothalamic NPY levels. In lean satiated rats CGP 71683A significantly antagonized the increase in food intake induced by intracerebroventricular injection of NPY. In 24-h fasted and streptozotocin diabetic rats CGP 71683A dose-dependently inhibited food intake. During the dark phase, CGP 71683A dose-dependently inhibited food intake in free-feeding lean rats without affecting the normal pattern of food intake or inducing taste aversion. In free-feeding lean rats, intraperitoneal administration of CGP 71683A for 28 d inhibited food intake dose-dependently with a maximum reduction observed on days 3 and 4. Despite the return of food intake to control levels, body weight and the peripheral fat mass remained significantly reduced. The data demonstrate that the NPY Y5 receptor subtype plays a role in NPY-induced food intake, but also suggest that, with chronic blockade, counterregulatory mechanisms are induced to restore appetite.

Authors

L Criscione, P Rigollier, C Batzl-Hartmann, H Rüeger, A Stricker-Krongrad, P Wyss, L Brunner, S Whitebread, Y Yamaguchi, C Gerald, R O Heurich, M W Walker, M Chiesi, W Schilling, K G Hofbauer, N Levens

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Agonist internalization by cloned Y1 neuropeptide Y (NPY) receptor in Chinese hamster ovary cells shows strong preference for NPY, endosome-linked entry and fast receptor recycling
SL Parker, MS Parker, I Lundell, A Balasubramaniam, A Buschauer, JK Kane, A Yalcin, MM Berglund 		Regulatory Peptides 2002
Food intake inhibition and reduction in body weight gain in lean and obese rodents treated with GW438014A, a potent and selective NPY-Y5 receptor antagonist
AJ Daniels, MK Grizzle, RP Wiard, JE Matthews, D Heyer 		Regulatory Peptides 2002
Effects of a high-fat diet and strain on hypothalamic gene expression in rats
AO Schaffhauser, AM Madiehe, HD Braymer, GA Bray, DA York 		Obesity research 2002
Selective Antagonism of the NPY Y5 Receptor Does Not Have a Major Effect on Feeding in Rats
AV Turnbull, L Ellershaw, DJ Masters, S Birtles, S Boyer, D Carroll, P Clarkson, SJ Loxham, P McAulay, JL Teague, KM Foote, JE Pease, MH Block 		Diabetes 2002
Changes in UCP2, PPARγ2, and C/EBPα Gene Expression Induced by a Neuropeptide Y (NPY) Related Receptor Antagonist in Overweight Rats
J Margareto, I Rivero, A Monge, I Aldana, A Marti, JA Martínez 		Nutritional Neuroscience 2002
Appetite suppression based on selective inhibition of NPY receptors
S Chamorro, O Della-Zuana, JL Fauchère, M Félétou, JP Galizzi, N Levens 		International Journal of Obesity 2002
The impact of the leucine 7 to proline 7 polymorphism of the neuropeptide Y gene on postprandial lipemia and on the response of serum total and lipoprotein lipids to a reduced fat diet
US Schwab, JJ Ågren, R Valve, MA Hallikainen, ES Sarkkinen, M Jauhiainen, MK Karvonen, U Pesonen, M Koulu, MI Uusitupa, MJ Savolainen 		European Journal of Clinical Nutrition 2002
Drug Discovery and Evaluation
HG Vogel, WH Vogel, BA Schölkens, J Sandow, G Müller, WF Vogel 		2002
Pharmacological Approaches for the Treatment of Obesity:
JA Fernndez-Lpez, X Remesar, M Foz, M Alemany 		Drugs 2002
Multiple NPY Receptors Inhibit GABAA Synaptic Responses of Rat Medial Parvocellular Effector Neurons in the Hypothalamic Paraventricular Nucleus
N Pronchuk, AG Beck-Sickinger, WF Colmers 		Endocrinology 2002
Key Motif to Gain Selectivity at the Neuropeptide Y 5 -Receptor: Structure and Dynamics of Micelle-Bound [Ala 31 , Pro 32 ]-NPY ,
R Bader, G Rytz, M Lerch, AG Beck-Sickinger, O Zerbe 		Biochemistry 2002
Ala 31 -Aib 32 : Identification of the Key Motif for High Affinity and Selectivity of Neuropeptide Y at the Y 5 -Receptor
C Cabrele, HA Wieland, N Koglin, C Stidsen, AG Beck-Sickinger 		Biochemistry 2002
Discovery and Optimization of a Series of Carbazole Ureas as NPY5 Antagonists for the Treatment of Obesity
MH Block, S Boyer, W Brailsford, DR Brittain, D Carroll, S Chapman, DS Clarke, CS Donald, KM Foote, L Godfrey, A Ladner, PR Marsham, DJ Masters, CD Mee, MR O'Donovan, JE Pease, AG Pickup, JW Rayner, A Roberts, P Schofield, A Suleman, AV Turnbull 		Journal of Medicinal Chemistry 2002
Fasting, Leptin Treatment, and Glucose Administration Differentially Regulate Y1 Receptor Gene Expression in the Hypothalamus of Transgenic Mice
F Zammaretti, GC Panzica, C Eva 		Endocrinology 2001
Drug treatment of obesity: from past failures to future successes?
P Collins, G Williams 		British Journal of Clinical Pharmacology 2001
Pharmacotherapy of obesity: targets and perspectives
M Chiesi, C Huppertz, KG Hofbauer 		Trends in Pharmacological Sciences 2001
Identification of NPY-induced c-Fos expression in hypothalamic neurones projecting to the dorsal vagal complex and the lower thoracic spinal cord
MC Vi�uela, PJ Larsen 		The Journal of Comparative Neurology 2001
Chronic administration of neuropeptide Y into the lateral ventricle of C57BL/6J male mice produces an obesity syndrome including hyperphagia, hyperleptinemia, insulin resistance, and hypogonadism
PD Raposinho, DD Pierroz, P Broqua, RB White, T Pedrazzini, ML Aubert 		Molecular and Cellular Endocrinology 2001
Food intake inhibition and reduction in body weight gain in rats treated with GI264879A, a non-selective NPY-Y1 receptor antagonist
AJ Danielsa, WT Chance, MK Grizzle, D Heyer, JE Matthews 		Peptides 2001
Feeding after fourth ventricular administration of neuropeptide Y receptor agonists in rats
ES Corpa, J McQuade, S Krasnicki, DB Conze 		Peptides 2001
The mPVN mediates blockade of NPY-induced feeding by a Y5 receptor antagonist: a c-FOS analysis
M Yokosuka, MG Dube, PS Kalra, SP Kalra 		Peptides 2001
Multiple Y receptors mediate pancreatic polypeptide responses in mouse colon mucosa
HM Cox, EL Pollock, IR Tough, H Herzog 		Peptides 2001
Cloning and characterization of Rhesus monkey neuropeptide Y receptor subtypes
DR Gehlert, P Yang, C George, Y Wang, D Schober, S Gackenheimer, D Johnson, LS Beavers, RA Gadski, M Baez 		Peptides 2001
Blockade of pancreatic polypeptide-sensitive neuropeptide Y (NPY) receptors by agonist peptides is prevented by modulators of sodium transport. Implications for receptor signaling and regulation
MS Parker, MM Berglund, I Lundell, SL Parker 		Peptides 2001
Neuropeptide Y Y5 receptor antagonist CGP71683A: the effects on food intake and anxiety-related behavior in the rat
A Kask, E Vasar, LT Heidmets, L Allikmets, JE Wikberg 		European Journal of Pharmacology 2001
Aminopyrazoles with high affinity for the human neuropeptide Y5 receptor
CP Kordik, C Luo, BC Zanoni, SL Dax, JJ McNally, TW Lovenberg, SJ Wilson, AB Reitz 		Bioorganic & Medicinal Chemistry Letters 2001
Pyrazolecarboxamide human neuropeptide Y5 receptor ligands with in vivo antifeedant activity
CP Kordik, C Luo, BC Zanoni, TW Lovenberg, SJ Wilson, AH Vaidya, JJ Crooke, DI Rosenthal, AB Reitz 		Bioorganic & Medicinal Chemistry Letters 2001
Central Administration of BIBP3226, Neuropeptide Y (NPY) Y1 Receptor Antagonist, does not Inhibit Fasting- and NPY-Induced Food Intake in Neonatal Chicks
S Kawakami, R Ando, T Bungo, A Ohgushi, T Tachibana, DM Denbow, M Furuse 		The Journal of Poultry Science 2001
Novel analogues of neuropeptide Y with a preference for the Y1-receptor
RM S������ll, MC Dinger, I Lundell, D Larhammer, AG Beck-Sickinger 		European Journal of Biochemistry 2001
Neuropeptide-Y in the paraventricular nucleus increases ethanol self-administration
S P Kelley, M A Nannini, A M Bratt, C W Hodge 		Peptides 2001
Reduced food intake in response to CGP 71683A may be due to mechanisms other than NPY Y5 receptor blockade
OD Zuana, M Sadlo, M Germain, M Félétou, S Chamorro, F Tisserand, C Montrion, JF Boivin, J Duhault, JA Boutin, N Levens 		International Journal of Obesity 2001
Molecular characterization of the ligand-receptor interaction of the neuropeptide Y family
C Cabrele, AG Beck-Sickinger 		Journal of Peptide Science 2000
Neuropeptides as emerging targets in anorexia and cachexia
A Asakawa, A Inui 		Expert Opinion on Therapeutic Targets 2000
BIIE0246, a potent and highly selective non-peptide neuropeptide Y Y(2) receptor antagonist
Y Dumont, A Cadieux, H Doods, LH Pheng, R Abounader, E Hamel, D Jacques, D Regoli, R Quirion 		British Journal of Pharmacology 2000
Corticotropin releasing hormone neurons in the paraventricular nucleus are direct targets for neuropeptide Y neurons in the arcuate nucleus: an anterograde tracing study
C Li, P Chen, MS Smith 		Brain Research 2000
L-152,804: Orally Active and Selective Neuropeptide Y Y5 Receptor Antagonist
A Kanatani, A Ishihara, H Iwaasa, K Nakamura, O Okamoto, M Hidaka, J Ito, T Fukuroda, DJ MacNeil, LH van der Ploeg, Y Ishii, T Okabe, T Fukami, M Ihara 		Biochemical and Biophysical Research Communications 2000
Patent focus on new anti-obesity agents: September 1999 - February 2000
PA Carpino 		Expert Opinion on Therapeutic Patents 2000
Orexin-induced food intake involves neuropeptide Y pathway
A Yamanaka, K Kunii, T Nambu, N Tsujino, A Sakai, I Matsuzaki, Y Miwa, K Goto, T Sakurai 		Brain Research 2000
N-Acylated α-(3-pyridylmethyl)-β-aminotetralin antagonists of the human neuropeptide Y Y5 receptor
JJ McNally, MA Youngman, TW Lovenberg, D Nepomuceno, S Wilson, SL Dax 		Bioorganic & Medicinal Chemistry Letters 2000
Design, synthesis and SAR of a series of 2-substituted 4-amino-quinazoline neuropeptide Y Y5 receptor antagonists
H Rueeger, P Rigollier, Y Yamaguchi, T Schmidlin, W Schilling, L Criscione, S Whitebread, M Chiesi, MW Walker, D Dhanoa, I Islam, J Zhang, C Gluchowski 		Bioorganic & Medicinal Chemistry Letters 2000
N-(Sulfonamido)alkyl[tetrahydro-1H-benzo[e]indol-2-yl]amines: potent antagonists of human neuropeptide Y Y5 receptor
JJ McNally, MA Youngman, TW Lovenberg, DH Nepomuceno, SJ Wilson, SL Dax 		Bioorganic & Medicinal Chemistry Letters 2000
Behavioral characterization of neuropeptide Y knockout mice
AW Bannon, J Seda, M Carmouche, JM Francis, MH Norman, B Karbon, ML McCaleb 		Brain Research 2000
Nicotine administration enhances NPY expression in the rat hypothalamus
MD Li, JK Kane, SL Parker, K McAllen, SG Matta, BM Sharp 		Brain Research 2000
Evidence of NPY Y5 receptor involvement in food intake elicited by orexin A in sated rats
MG Dube, TL Horvath, PS Kalra, SP Kalra 		Peptides 2000
[D-Trp34] neuropeptide Y is a potent and selective neuropeptide Y Y5 receptor agonist with dramatic effects on food intake☆
EM Parker, A Balasubramaniam, M Guzzi, DE Mullins, BG Salisbury, S Sheriff, MB Witten, JJ Hwa 		Peptides 2000
The hypothalamus and the regulation of energy homeostasis: lifting the lid on a black box
G Williams, JA Harrold, DJ Cutler 		Proceedings of the Nutrition Society 2000
Association of neuropeptide Y Y1 receptors with glutamate-positive and NPY-positive neurons in rat hippocampal cultures
JA St-Pierre, D Nouel, Y Dumont, A Beaudet, R Quirion 		European Journal of Neuroscience 2000
Potent and selective tools to investigate neuropeptide Y receptors in the central and peripheral nervous systems: BIBO3304 (Y1) and CGP71683A (Y5)
Y Dumont, A Cadieux, H Doods, A Fournier, R Quirion 		Canadian Journal of Physiology and Pharmacology 2000
PYY preference is a common characteristic of neuropeptide Y receptors expressed in human, rat, and mouse gastrointestinal epithelia
ND Holliday, EL Pollock, IR Tough, HM Cox 		Canadian Journal of Physiology and Pharmacology 2000
Orexigenic effect of the melanocortin MC4receptor antagonist HS014 is inhibited only partially by neuropeptide Y Y1receptor selective antagonists
A Kask, HB Schiöth, J Harro, JE Wikberg, L Rägo 		Canadian Journal of Physiology and Pharmacology 2000
Food intake regulation in rodents: Y5or Y1NPY receptors or both?
J Duhault, M Boulanger, S Chamorro, JA Boutin, OD Zuana, E Douillet, JL Fauchère, M Félétou, M Germain, B Husson, AM Vega, P Renard, F Tisserand 		Canadian Journal of Physiology and Pharmacology 2000
NPY-Ergic agents for the treatment of obesity
IA Zim�nyi, GS Poindexter 		Drug Development Research 2000
Pharmacological characterization of the cloned neuropeptide Y y6 receptor
DE Mullins, M Guzzi, L Xia, EM Parker 		European Journal of Pharmacology 2000
The role of NPY in metabolic homeostasis: implications for obesity therapy
HA Wieland, BS Hamilton, B Krist, HN Doods 		Expert Opinion on Investigational Drugs 2000
Leptin effects on pulsatile gonadotropin releasing hormone secretion from the adult rat hypothalamus and interaction with cocaine and amphetamine regulated transcript peptide and neuropeptide Y
AS Parent, MC Lebrethon, A Gérard, E Vandersmissen, JP Bourguignon 		Regulatory Peptides 2000
Evidence that NPY Y1 receptors are involved in stimulation of feeding by orexins (hypocretins) in sated rats
MR Jain, TL Horvath, PS Kalra, SP Kalra 		Regulatory Peptides 2000
Neuropeptide Y–Y1 receptor antisense oligodeoxynucleotide increases the infarct volume after middle cerebral artery occlusion in rats
RT Cheung, DF Cechetto 		Neuroscience 2000
The First Selective Agonist for the Neuropeptide YY 5 Receptor Increases Food Intake in Rats
C Cabrele, M Langer, R Bader, HA Wieland, HN Doods, O Zerbe, AG Beck-Sickinger 		The Journal of biological chemistry 2000
Novel polymorphisms in the neuropeptide-Y Y5 receptor associated with obesity in Pima Indians
CP Jenkinson, K Cray, K Walder, H Herzog, R Hanson, E Ravussin 		International Journal of Obesity 2000
Transgenic study of energy homeostasis equation: implications and confounding influences
A Inui 		The FASEB Journal 2000
Endoscopic Gastric Surgery
E Hanisch, M Kitajima, T Wehrmann, A Encke 		2000
Promising New Approaches to the Management of Obesity:
IL Mertens, LF Gaal 		Drugs 2000
α-Substituted N -(Sulfonamido)alkyl-β-aminotetralins: Potent and Selective Neuropeptide Y Y5 Receptor Antagonists
MA Youngman, JJ McNally, TW Lovenberg, AB Reitz, NM Willard, DH Nepomuceno, SJ Wilson, JJ Crooke, D Rosenthal, AH Vaidya, SL Dax 		Journal of Medicinal Chemistry 2000
Regulation of Feeding-Associated Peptides and Receptors by Nicotine
MD Li, SL Parker, JK Kane 		Molecular Neurobiology 2000
Multiple receptors for neuropeptide Y in the hippocampus: putative roles in seizures and cognition
JP Redrobe, Y Dumont, JA St-Pierre, R Quirion 		Brain Research 1999
BIIE0246: A selective and high affinity neuropeptide Y Y2 receptor antagonist
H Doods, W Gaida, HA Wieland, H Dollinger, G Schnorrenberg, F Esser, W Engel, W Eberlein, K Rudolf 		European Journal of Pharmacology 1999
Regulation of Neuropeptide Y Release by Neuropeptide Y Receptor Ligands and Calcium Channel Antagonists in Hypothalamic Slices
PJ King, PS Widdowson, HN Doods, G Williams 		Journal of Neurochemistry 1999
Extensive Alternative Splicing in the 5′-Untranslated Region of the Rat and Human Neuropeptide Y Y5 Receptor Genes Regulates Receptor Expession
EM Parker, L Xia 		Journal of Neurochemistry 1999
Role of hypothalamic neuropeptide Y in feeding and obesity
DR Gehlert 		Neuropeptides 1999
Activation of central neuropeptide Y Y1 receptors potently stimulates food intake in male rhesus monkeys
PJ Larsen, M Tang-Christensen, CE Stidsen, K Madsen, MS Smith, JL Cameron 		The Journal of clinical endocrinology and metabolism 1999
Inhibition of Neuropeptide Y (NPY)-Induced Feeding and c-Fos Response in Magnocellular Paraventricular Nucleus by a NPY Receptor Antagonist: A Site of NPY Action1
M Yokosuka, PS Kalra, SP Kalra 		Endocrinology 1999
NPY receptor subtype in the rabbit isolated ileum.
Félétou M, Nicolas JP, Rodriguez M, Beauverger P, Galizzi JP, Boutin JA, Duhault J 		British Journal of Pharmacology 1999
Handbook of Chemical Neuroanatomy
DF Swaab 		Handbook of Chemical Neuroanatomy 1997

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