help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kanatani, A.
Right arrow Articles by Ihara, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kanatani, A.
Right arrow Articles by Ihara, M.

Endocrinology, Vol 137, 3177-3182, Copyright © 1996 by Endocrine Society

ARTICLES

Potent neuropeptide Y Y1 receptor antagonist, 1229U91: blockade of neuropeptide Y-induced and physiological food intake

A Kanatani, A Ishihara, S Asahi, T Tanaka, S Ozaki and M Ihara
Tsukuba Research Institute, Banyu Pharmaceutical Co., Japan.

Neuropeptide Y (NPY) is thought to increase food intake through the action of Y1 (-like) receptors in the hypothalamus. To confirm the involvement of Y1 receptors in feeding behavior, selective and potent antagonists for Y1 receptors are required. In the present study, we showed that a peptide, 1229U91 [(Ile,Glu,Pro,Dpr,Tyr,Arg,Leu,Arg, Tyr- NH2)2 cyclic (2,4'),(2',4)-diamide], is a potent and selective antagonist for Y1 receptors. 1229U91 displaced [125I]peptide YY (PYY) binding to membranes of human neuroblastoma-derived SK-N-MC cells that predominantly express Y1 receptors with a K1 value 0.10 nM and inhibited the NPY-induced increase in intracellular calcium levels(IC50 = 0.27 nM). In contrast, the K1 values for [125I]PYY binding to Y2 receptors in membranes of human neuroblastoma-derived SK-N-BE2 cells and rat hypothalamus were 700 nM and more than 1 microM, respectively. Although [125I]PYY could not detect Y1 receptors in the rat hypothalamic membranes, [125I]1229U91 revealed binding sites with a high affinity (Kd = 18 pM), indicating the presence of Y1 receptors in the hypothalamus. Intracerebroventricular injection of 1229U91 (30 micrograms) into male Sprague-Dawley rats completely inhibited NPY (5 micrograms)-induced food intake without any other behavioral change. Furthermore, intracerebroventricular injection of 1229U91 significantly suppressed physiological feeding behavior after overnight fasting. These results indicate that Y1 receptors in the rat hypothalamus mediate NPY-induced food intake, and that physiological feeding behavior after overnight fasting may be largely regulated by NPY via Y1 receptors. 1229U91 may be useful for further elucidating the pathophysiological roles of NPY in feeding behavior.


This article has been cited by other articles:


Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
J. Dark and K. M. Pelz
NPY Y1 receptor antagonist prevents NPY-induced torporlike hypothermia in cold-acclimated Siberian hamsters
Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2008; 294(1): R236 - R245.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
M. M. Kamiji and A. Inui
Neuropeptide Y Receptor Selective Ligands in the Treatment of Obesity
Endocr. Rev., October 1, 2007; 28(6): 664 - 684.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
F. Zammaretti, G. Panzica, and C. Eva
Sex-dependent regulation of hypothalamic neuropeptide Y-Y1 receptor gene expression in moderate/high fat, high-energy diet-fed mice
J. Physiol., September 1, 2007; 583(2): 445 - 454.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
B. Sloth, J. J. Holst, A. Flint, N. T. Gregersen, and A. Astrup
Effects of PYY1-36 and PYY3-36 on appetite, energy intake, energy expenditure, glucose and fat metabolism in obese and lean subjects
Am J Physiol Endocrinol Metab, April 1, 2007; 292(4): E1062 - E1068.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
E. Keen-Rhinehart and T. J. Bartness
NPY Y1 receptor is involved in ghrelin- and fasting-induced increases in foraging, food hoarding, and food intake
Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2007; 292(4): R1728 - R1737.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
E.-J. D. Lin, A. Sainsbury, N. J. Lee, D. Boey, M. Couzens, R. Enriquez, K. Slack, R. Bland, M. J. During, and H. Herzog
Combined Deletion of Y1, Y2, and Y4 Receptors Prevents Hypothalamic Neuropeptide Y Overexpression-Induced Hyperinsulinemia despite Persistence of Hyperphagia and Obesity
Endocrinology, November 1, 2006; 147(11): 5094 - 5101.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
S. Stanley, K. Wynne, B. McGowan, and S. Bloom
Hormonal Regulation of Food Intake
Physiol Rev, October 1, 2005; 85(4): 1131 - 1158.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
L. F. Faulconbridge, H. J. Grill, and J. M. Kaplan
Distinct Forebrain and Caudal Brainstem Contributions to the Neuropeptide Y Mediation of Ghrelin Hyperphagia
Diabetes, July 1, 2005; 54(7): 1985 - 1993.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
K. Wynne, S. Stanley, B. McGowan, and S. Bloom
Appetite control
J. Endocrinol., February 1, 2005; 184(2): 291 - 318.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
N. R. Vulliemoz, E. Xiao, L. Xia-Zhang, S. L. Wardlaw, and M. Ferin
Central Infusion of Agouti-Related Peptide Suppresses Pulsatile Luteinizing Hormone Release in the Ovariectomized Rhesus Monkey
Endocrinology, February 1, 2005; 146(2): 784 - 789.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
I. J. Clarke, K. Backholer, and A. J. Tilbrook
Y2 Receptor-Selective Agonist Delays the Estrogen-Induced Luteinizing Hormone Surge in Ovariectomized Ewes, but Y1-Receptor-Selective Agonist Stimulates Voluntary Food Intake
Endocrinology, February 1, 2005; 146(2): 769 - 775.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
T. Karl, S. Lin, C. Schwarzer, A. Sainsbury, M. Couzens, W. Wittmann, D. Boey, S. von Horsten, and H. Herzog
Y1 receptors regulate aggressive behavior by modulating serotonin pathways
PNAS, August 24, 2004; 101(34): 12742 - 12747.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
P. D. Raposinho, T. Pedrazzini, R. B. White, R. D. Palmiter, and M. L. Aubert
Chronic Neuropeptide Y Infusion into the Lateral Ventricle Induces Sustained Feeding and Obesity in Mice Lacking Either Npy1r or Npy5r Expression
Endocrinology, January 1, 2004; 145(1): 304 - 310.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
J. W. Hill and J. E. Levine
Abnormal Response of the Neuropeptide Y-Deficient Mouse Reproductive Axis to Food Deprivation But Not Lactation
Endocrinology, May 1, 2003; 144(5): 1780 - 1786.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
K. Toshinai, Y. Date, N. Murakami, M. Shimada, M. S. Mondal, T. Shimbara, J.-L. Guan, Q.-P. Wang, H. Funahashi, T. Sakurai, et al.
Ghrelin-Induced Food Intake Is Mediated via the Orexin Pathway
Endocrinology, April 1, 2003; 144(4): 1506 - 1512.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
N. Pronchuk, A. G. Beck-Sickinger, and W. F. Colmers
Multiple NPY Receptors Inhibit GABAA Synaptic Responses of Rat Medial Parvocellular Effector Neurons in the Hypothalamic Paraventricular Nucleus
Endocrinology, February 1, 2002; 143(2): 535 - 543.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
C. L. Chaffer and M. J. Morris
The Feeding Response to Melanin-Concentrating Hormone Is Attenuated by Antagonism of the NPY Y1-Receptor in the Rat
Endocrinology, January 1, 2002; 143(1): 191 - 197.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
F. Zammaretti, G. Panzica, and C. Eva
Fasting, Leptin Treatment, and Glucose Administration Differentially Regulate Y1 Receptor Gene Expression in the Hypothalamus of Transgenic Mice
Endocrinology, September 1, 2001; 142(9): 3774 - 3782.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
D. Mullins, D. Kirby, J. Hwa, M. Guzzi, J. Rivier, and E. Parker
Identification of Potent and Selective Neuropeptide Y Y1 Receptor Agonists with Orexigenic Activity in Vivo
Mol. Pharmacol., September 1, 2001; 60(3): 534 - 540.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
A. Kanatani, M. Hata, S. Mashiko, A. Ishihara, O. Okamoto, Y. Haga, T. Ohe, T. Kanno, N. Murai, Y. Ishii, et al.
A Typical Y1 Receptor Regulates Feeding Behaviors: Effects of a Potent and Selective Y1 Antagonist, J-115814
Mol. Pharmacol., March 1, 2001; 59(3): 501 - 505.
[Abstract] [Full Text]

Home page
 J. Neurosci.Home page
M. Shimizu-Albergine, D. L. Ippolito, and J. A. Beavo
Downregulation of Fasting-Induced cAMP Response Element-Mediated Gene Induction by Leptin in Neuropeptide Y Neurons of the Arcuate Nucleus
J. Neurosci., February 15, 2001; 21(4): 1238 - 1246.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
D. A. Schober, S. L. Gackenheimer, M. L. Heiman, and D. R. Gehlert
Pharmacological Characterization of 125I-1229U91 Binding to Y1 and Y4 Neuropeptide Y/Peptide YY Receptors
J. Pharmacol. Exp. Ther., April 1, 2000; 293(1): 275 - 280.
[Abstract] [Full Text]

Home page
 Pharmacol. Rev.Home page
A. Inui
Transgenic Approach to the Study of Body Weight Regulation
Pharmacol. Rev., March 1, 2000; 52(1): 35 - 62.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
G. A. Bray and F. L. Greenway
Current and Potential Drugs for Treatment of Obesity
Endocr. Rev., December 1, 1999; 20(6): 805 - 875.
[Abstract] [Full Text]

Home page
 EndocrinologyHome page
M. R. Jain, S. Pu, P. S. Kalra, and S. P. Kalra
Evidence that Stimulation of Two Modalities of Pituitary Luteinizing Hormone Release in Ovarian Steroid-Primed Ovariectomized Rats May Involve Neuropeptide Y Y1 and Y4 Receptors
Endocrinology, November 1, 1999; 140(11): 5171 - 5177.
[Abstract] [Full Text]

Home page
 J. Clin. Endocrinol. Metab.Home page
P. J. Larsen, M. Tang-Christensen, C. E. Stidsen, K. Madsen, M. S. Smith, and J. L. Cameron
Activation of Central Neuropeptide Y Y1 Receptors Potently Stimulates Food Intake in Male Rhesus Monkeys
J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3781 - 3791.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
M. Yokosuka, P. S. Kalra, and S. P. Kalra
Inhibition of Neuropeptide Y (NPY)-Induced Feeding and c-Fos Response in Magnocellular Paraventricular Nucleus by a NPY Receptor Antagonist: A Site of NPY Action
Endocrinology, October 1, 1999; 140(10): 4494 - 4500.
[Abstract] [Full Text]

Home page
 J. Pharmacol. Exp. Ther.Home page
S. Iyengar, D. L. Li, and R. M. A. Simmons
Characterization of Neuropeptide Y-Induced Feeding in Mice: Do Y1-Y6 Receptor Subtypes Mediate Feeding?
J. Pharmacol. Exp. Ther., May 1, 1999; 289(2): 1031 - 1040.
[Abstract] [Full Text]

Home page
 J. Neurophysiol.Home page
L. Sun and R. J. Miller
Multiple Neuropeptide Y Receptors Regulate K+ and Ca2+ Channels in Acutely Isolated Neurons From the Rat Arcuate Nucleus
J Neurophysiol, March 1, 1999; 81(3): 1391 - 1403.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
S. P. Kalra, M. G. Dube, S. Pu, B. Xu, T. L. Horvath, and P. S. Kalra
Interacting Appetite-Regulating Pathways in the Hypothalamic Regulation of Body Weight
Endocr. Rev., February 1, 1999; 20(1): 68 - 100.
[Abstract] [Full Text]

Home page
 EndocrinologyHome page
S. Pu, M. R. Jain, T. L. Horvath, S. Diano, P. S. Kalra, and S. P. Kalra
Interactions between Neuropeptide Y and {gamma}-Aminobutyric Acid in Stimulation of Feeding: A Morphological and Pharmacological Analysis
Endocrinology, February 1, 1999; 140(2): 933 - 940.
[Abstract] [Full Text]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. Kushi, H. Sasai, H. Koizumi, N. Takeda, M. Yokoyama, and M. Nakamura
Obesity and mild hyperinsulinemia found in neuropeptide Y-Y1 receptor-deficient mice
PNAS, December 22, 1998; 95(26): 15659 - 15664.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
Y. Dumont, A. Fournier, and R. Quirion
Expression and Characterization of the Neuropeptide Y Y5 Receptor Subtype in the Rat Brain
J. Neurosci., August 1, 1998; 18(15): 5565 - 5574.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
A. Ishihara, T. Tanaka, A. Kanatani, T. Fukami, M. Ihara, and T. Fukuroda
A potent neuropeptide Y antagonist, 1229U91, suppressed spontaneous food intake in Zucker fatty rats
Am J Physiol Regulatory Integrative Comp Physiol, May 1, 1998; 274(5): R1500 - R1504.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
B. Xu, M. G. Dube, P. S. Kalra, W. G. Farmerie, A. Kaibara, L. L. Moldawer, D. Martin, and S. P. Kalra
Anorectic Effects of the Cytokine, Ciliary Neurotropic Factor, Are Mediated by Hypothalamic Neuropeptide Y: Comparison with Leptin
Endocrinology, February 1, 1998; 139(2): 466 - 473.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. Cabrele, M. Langer, R. Bader, H. A. Wieland, H. N. Doods, O. Zerbe, and A. G. Beck-Sickinger
The First Selective Agonist for the Neuropeptide YY5 Receptor Increases Food Intake in Rats
J. Biol. Chem., November 10, 2000; 275(46): 36043 - 36048.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1996 by The Endocrine Society