| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
ARTICLES |
Tsukuba Research Institute in collaboration with Merck Research Laboratories, Banyu Pharmaceutical Co., Ltd. (A.K., S.M., N.M., N.S., J.I., T.Fuku, T.Fuka., Y.S., S.N., M.I.), Okubo 3, Tsukuba 300-2611, Japan; and Merck Research Laboratories, Merck & Co., Inc. (N.M., D.J.M., L.H.T.V.d.P.), Rahway, New Jersey 07065
Address all correspondence and requests for reprints to: Dr. Akio Kanatani, Tsukuba Research Institute, Banyu Pharmaceutical Co. Ltd., Okubo 3, Tsukuba 300-2611, Japan. E-mail: kantniak{at}banyu.co.jp
Neuropeptide Y (NPY) increases food intake through the action of hypothalamic NPY receptors. At least six subtypes of NPY, peptide YY (PYY), and pancreatic polypeptide (PP) receptors have been identified in mice. Although the involvement of Y1 and Y5 receptors in feeding regulation has been suggested, the relative importance of each of these NPY receptors and the participation of a novel feeding receptor are still unclear. To address this issue, we generated a Y1 receptor-deficient (Y1-/-) and a Y5 receptor-deficient (Y5-/-) mouse line in which we directly compared the orexigenic effects of NPY and its analogs after intracerebroventricular (icv) administration. The icv NPY-induced food intake was remarkably reduced in Y1-/- mice, but was not significantly altered by inactivation of the Y5 receptor. The Y1 receptor therefore plays a dominant role in NPY-induced feeding. Stimulation of feeding by moderately selective Y5 agonists [PYY-(3–36), human PP, and bovine PP] was reduced in Y5-/- mice, although food intake did not decrease to vehicle control levels. These results indicate that the Y5 receptor functions as one of the feeding receptors. In addition, the finding that Y5-preferring agonists still induce food intake in Y5-/- mice suggests a role for another NPY receptor(s), including the possibility of novel NPY receptors. Surprisingly, despite the limited efficacy of PYY-(3–36) and PPs at the Y1 receptor, food consumption induced by these agonists was significantly diminished in Y1-/- mice compared with that in wild-type controls. These observations suggest that the feeding stimulation induced by NPY and its analogs may be directly or indirectly modulated by the action of the Y1 receptor. We conclude that multiple NPY receptors, possibly including the novel feeding receptor, are involved in the feeding response evoked by NPY and its analogs. Among them, the Y1 receptor plays a key role in NPY-induced feeding in mice.
This article has been cited by other articles:
 |
|
 |
|
  E. Karra, K. Chandarana, and R. L. Batterham The role of peptide YY in appetite regulation and obesity J. Physiol., January 1, 2009; 587(1): 19 - 25. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Ortiz, L. F. Milardo, L. B. DeCarr, T. M. Buckholz, M. R. Mays, T. H. Claus, J. N. Livingston, C. D. Mahle, and K. J. Lumb A Novel Long-Acting Selective Neuropeptide Y2 Receptor Polyethylene Glycol-Conjugated Peptide Agonist Reduces Food Intake and Body Weight and Improves Glucose Metabolism in Rodents J. Pharmacol. Exp. Ther., November 1, 2007; 323(2): 692 - 700. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 G. L. Rahardjo, X.-F. Huang, Y. Y. Tan, and C. Deng Decreased Plasma Peptide YY Accompanied by Elevated Peptide YY and Y2 Receptor Binding Densities in the Medulla Oblongata of Diet-Induced Obese Mice Endocrinology, October 1, 2007; 148(10): 4704 - 4710. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 S. Mashiko, A. Ishihara, H. Iwaasa, H. Sano, J. Ito, A. Gomori, Z. Oda, R. Moriya, H. Matsushita, M. Jitsuoka, et al. A Pair-Feeding Study Reveals That a Y5 Antagonist Causes Weight Loss in Diet-Induced Obese Mice by Modulating Food Intake and Energy Expenditure Mol. Pharmacol., February 1, 2007; 71(2): 602 - 608. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 B Beck Neuropeptide Y in normal eating and in genetic and dietary-induced obesity Phil Trans R Soc B, July 29, 2006; 361(1471): 1159 - 1185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Chaudhri, C. Small, and S. Bloom Gastrointestinal hormones regulating appetite Phil Trans R Soc B, July 29, 2006; 361(1471): 1187 - 1209. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ishihara, A. Kanatani, S. Mashiko, T. Tanaka, M. Hidaka, A. Gomori, H. Iwaasa, N. Murai, S.-i. Egashira, T. Murai, et al. A neuropeptide Y Y5 antagonist selectively ameliorates body weight gain and associated parameters in diet-induced obese mice PNAS, May 2, 2006; 103(18): 7154 - 7158. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 K. Wynne, S. Stanley, B. McGowan, and S. Bloom Appetite control J. Endocrinol., February 1, 2005; 184(2): 291 - 318. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 K.G. Murphy and S.R. Bloom Gut hormones in the control of appetite Exp Physiol, September 1, 2004; 89(5): 507 - 516. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Wynne, S. Stanley, and S. Bloom The Gut and Regulation of Body Weight J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2576 - 2582. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 U. Nordheim and K. G. Hofbauer Stimulation of NPY Y2 receptors by PYY3-36 reveals divergent cardiovascular effects of endogenous NPY in rats on different dietary regimens Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2004; 286(1): R138 - R142. [Abstract] [Full Text]
|
|
|
|
|
|
S. Mashiko, A. Ishihara, H. Iwaasa, H. Sano, Z. Oda, J. Ito, M. Yumoto, M. Okawa, J. Suzuki, T. Fukuroda, et al. Characterization of Neuropeptide Y (NPY) Y5 Receptor-Mediated Obesity in Mice: Chronic Intracerebroventricular Infusion of D-Trp34NPY Endocrinology, May 1, 2003; 144(5): 1793 - 1801. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 M. M. Berglund, P. A. Hipskind, and D. R. Gehlert Recent Developments in Our Understanding of the Physiological Role of PP-Fold Peptide Receptor Subtypes Experimental Biology and Medicine, March 1, 2003; 228(3): 217 - 244. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. V. Turnbull, L. Ellershaw, D. J. Masters, S. Birtles, S. Boyer, D. Carroll, P. Clarkson, S. J.G. Loxham, P. McAulay, J. L. Teague, et al. Selective Antagonism of the NPY Y5 Receptor Does Not Have a Major Effect on Feeding in Rats Diabetes, August 1, 2002; 51(8): 2441 - 2449. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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 | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
