| 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
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Five distinct types of G protein-coupled NPY receptors, Y1, Y2, Y4, Y5, and y6, have been cloned from mice (13). The Y5 receptor is proposed to be a feeding receptor based on the correlation between the in vitro functional and binding activities of different peptide agonists and their potent stimulation of food intake in rodent models (14). This hypothesis was supported by the finding that intracerebroventricular (icv) administration of Y5 receptor antisense oligonucleotides reduced food intake (15, 16). With regard to the Y1 receptors, specific Y1 antagonists suppressed feeding behaviors (17, 18, 19), indicating that the Y1 receptor is also involved in feeding regulation. In support of a model that proposes a role for both the Y1 and Y5 receptors in food intake, a reduction of food intake induced by NPY and related peptides has been reported in Y1 receptor-deficient and Y5 receptor-deficient mice (20, 21). However, these experiments were performed independently using genetically distinct NPY receptor-deficient mice and different NPY peptide ligands, making a head-on comparison of the effects of these ligands in each mouse strain difficult. Consequently, the performance of a direct comparative study in mice with a similar genetic background and under the same experimental conditions is crucial to evaluate the relative role of either the Y1 or the Y5 receptor in feeding regulation.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Vector construction and homologous recombination
Genomic clones for mouse Y1 receptor (clone 3) and Y5 receptor
(clone 17) were isolated by screening a genomic library established in
FixII from TT2 embryonic stem (ES) cell DNA with a
complementary DNA probe generated by a PCR strategy based on the
reported nucleotide sequences of the Y1 and Y5 receptors, respectively
(GenBank accession no. D63818 and AF022948). To construct the targeting
vector for the Y1 receptor, a 7.5-kb 5'-DNA fragment spanning from the
HindIII site to the end of genomic clone 3 was ligated with
the pgk-neo and pgk-DT cassette constructed in Bluescript
SK+ vector. A 1-kb
BamHI-ClaI fragment from the 3'-flanking region
was inserted between pgk-neo and pgk-DT to serve as a short arm. A
similar strategy was employed to construct the targeting vector for the
Y5 receptor. A 5-kb XbaI DNA fragment located 3' of the
genomic clone 17 was ligated with the pgk-neo-pgk-DT cassette. A 1-kb
DNA fragment spanning from the EcoRV site in the 5'-region
to the NcoI site in the first exon was inserted between
pgk-neo and pgk-DT to serve as a short arm. These vectors were
linearized at the NotI site located at the 3'-end of pgk-DT
and introduced into TT2 ES cells by electroporation [C57BL/6
(B6)/CBA] as described previously (22). After selection with G418,
resistant clones were picked up, and their DNA was analyzed by PCR
using a neo-specific primer PGK-R and Y1- or Y5-specific genomic
primers (Y1-R5 or Y5-L2, respectively). The sequences for these primers
were: PGK-R, 5'- CTAAAGCGCATGCTCCAGACT-3'; Y1-R5,
5'-CCATTGCCACCTCTCCACTCTTCTC-3'; and Y5-L2,
5'-GCTTACATCTGTAATAGAGTTC-TGAC-3'.
Generation of NPY receptor-deficient mice
Embryo manipulations and injection of the ES cell clones into
ICR 8 cell embryos were carried out as described previously
(22). Chimeric mice with a high contribution of TT2 genetic background
(monitored by agouti coat color) were bred with C57BL/6 mice. Genomic
DNA was prepared from the tails of offspring for genotyping by PCR
analysis. The mutant allele was detected by primers of PGK-R and Y1-R5
or Y5-L2, respectively. The PCR primers used to detect normal allele
were: Y1F, 5'-GAACTCAACTCTGTTCTCCAAGGTTG-3'; Y1R,
5'-ATGGCGGTGAGGTGACAGAGCAGAA-3'; Y5F,
5'-GTCTTGTTGGATCAGTGGATGTTTGGCA-3'; and Y5R,
5'-ATCAGTATGGTCAGTCTGTAGAAAACAC-3'. Northern blotting analysis of the
Y1 and Y5 mRNAs in the brain was also carried out using probes
generated by these primers to confirm the expression of the Y1 and Y5
transcripts.
icv peptide administration
Adult male mice (10–12 weeks old; 25–30 g) were maintained in
individual cages under controlled conditions of temperature (23 ±
2 C) and light-dark cycle (0700–1900 h). Water and pelleted food
(CE-2, CLEA, Tokyo, Japan) were available ad libitum.
Mice were anesthetized with sodium pentobarbital (80 mg/kg, ip;
Dinabot, Tokyo, Japan). A permanent 24-gauge stainless steel
cannula was stereotaxically implanted into the right lateral ventricle.
The stereotaxic coordinates used were as follows: 0.4 mm posterior, 0.8
mm lateral, and 1 mm ventral to the bregma. The placement of the
cannula was confirmed at the end of the experiments by injection of
0.5% Evans blue dye. Animals were allowed 1 week of recovery, and they
were handled daily with mock injection to avoid nonspecific stress.
Groups of 10–40 animals received icv injections of ligands in 5 µl
0.01 M PBS containing 0.05% BSA or the vehicle
alone by a 30-gauge stainless steel injector that projected 1.0 mm
below the tip of the cannula. Food intake experiments were performed
using satiated mice with a moderate high fat diet (Oriental, Tokyo,
Japan) in the beginning of the light phase to avoid the
influence of indigenous peptide. Mice were fed a palatable moderate
high fat diet during the dark phase before the experiments. After
confirming sufficient amounts of food intake in the mice, NPY family
peptides or vehicle were injected. After icv treatment, food intake was
measured for a 2-h period between 0830–1130 h.
All experimental procedures followed the Japanese Pharmacological Society Guidelines for Animal Use. Results are given as the mean ± SE. Statistical analysis was performed using ANOVA, followed by Bonferroni’s test.
Expression of mouse receptors in COS-7 cells and receptor binding
assays
The coding regions of mY1, mY2, mY4, mY5, and my6 (GenBank
accession nos. Z18280, D86238, U40189, AF022948, and U58367,
respectively) were cloned by PCR into the multiple cloning site of
pCI-neo (Promega Corp., Madison, WI) with an optimal Kozac
sequence, GCCGCCACC, before the ATG start codons. The nucleotide
sequences of the resulting clones were confirmed to be free of
PCR-induced errors with an ABI 373A automated sequencer
(Perkin-Elmer Corp., Norwalk, CT). DNA was transfected
into COS-7 cells, membranes were prepared, binding reactions were
performed, and the data were analyzed as described previously (29),
except that artificial cerebrospinal fluid (CSF) buffer
(Life Technologies, Inc./BRL, Gaithersburg, MD) was used
as the binding buffer. Artificial CSF buffer contained 1.5
mM CaCl2, 4 mM KCl, 120
mM NaCl, 1 mM MgCl2, and
25 mM NaHCO3.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
and 2A. In both cases,
most of the coding exons were replaced with the neomycin resistance
gene. The identity of PCR-positive ES cell clones was confirmed by
Southern blotting analysis. Heterozygous lines were established from
two independent ES clones for both genes (c120 and c206 for the Y1
receptor, c36 and c151 for the Y5 receptor), and these heterozygous
mice were bred to generate Y1-/- and
Y5-/- mice, respectively (Figs. 1B and 2B).
Their offspring were genotyped by PCR and confirmed to lack the Y1 and
Y5 receptor genes, respectively (Figs. 1C and 2C).
Y1-/- and Y5-/- mice
were live-born and had developed normally compared with the
heterozygotes or wild-type littermates (knockout mice were fertile and
exhibited slight obesity, as reported previously; other
deficiencies/abnormalities were not noted) (20, 21). Because the Y1 and
Y5 genes are known to be located within 40 kbp, in opposite orientation
on the same chromosome (23), we examined Y1-/-
and Y5-/- mice for the expression level of the
remaining intact NPY receptor. Northern blotting analysis was employed
to detect the Y1 and Y5 transcripts. The Y1 transcript could not be
detected in Y1-/- mice, whereas the Y5
transcript was indistinguishable from that of wild-type mice (Fig. 1D).
Similarly, Y5 expression could not be detected in
Y5-/- mice, in which Y1 expression was
indistinguishable from that in wild-type mice (Fig. 2D). Thus, we established individual
lines deficient for either the Y1 or the Y5 gene. Due to the close
proximity of the Y1 and Y5 genes, it is not practical to generate a
double (Y1 and Y5) knockout line by cross-breeding.
|
|
presents the affinities of the five
peptides used in the food intake studies at the cloned mouse NPY
receptors. The affinities were determined in artificial CSF buffer, as
the peptides were injected icv for the food intake studies. NPY has
high affinities for all subtypes of NPY receptors except the Y4
receptor. PYY-(3–36) has the highest affinities for the Y2 and Y5
receptors, with reduced affinities for all remaining subtypes.
PYY-(3–36) is only 3-fold less potent than NPY at the Y5 receptor, but
the affinity of PYY-(3–36) at the Y1 receptor was considerably
decreased (
40-fold compared with that of NPY). hPP and bPP showed
high affinities for both the Y4 and Y5 receptors, whereas rPP showed a
high affinity for only the Y4 receptor. Only NPY and PYY-(3–36) bound
to the mouse y6 receptor (8 and 24 nM, respectively).
|
, A and B). NPY-induced
feeding could still be observed in Y1-/- mice,
but the magnitude of food intake was significantly reduced in
Y1-/- mice compared with that in wild-type mice
(Fig. 3B). In contrast, NPY-induced
feeding was not affected in Y5-/- mice compared
with that in wild-type mice (Fig. 3B).
|
). PYY-(3–36)-induced feeding was significantly reduced in
Y5-/- mice. However, the remaining amount of
food intake was comparable to that observed with icv NPY-induced
feeding in wild-type mice (Fig. 3C). In addition, PYY-(3–36)-induced
feeding was also considerably suppressed in
Y1-/- mice compared with that in wild-type mice
(Fig. 3C).
PPs are agonists for Y4 receptors with subnanomolar binding affinities
(Table 1). hPP and bPP, but not rPP, also had relatively high
affinities for mouse Y5 receptors (Table 1). As expected from their
affinities at the Y5 receptor, both hPP and bPP elicited considerable
food intake, whereas rPP failed to show significant orexigenic effects
in wild-type mice (Fig. 3, D–F). hPP and bPP still induced a
significant level of food intake in Y5-/- mice,
but the amount of food intake was reduced compared with that in
wild-type mice (Fig. 3, D and E). Furthermore, as observed with
PYY-(3–36), the ingestive behavior evoked by PPs was reduced in
Y1-/- mice even though these peptides showed
low level efficacy at the Y1 receptor (based on their binding
affinities; Fig. 3, D and E, and Table 1).
Finally, U-50488 is a potent 
opioid receptor agonist known to
stimulate feeding behavior (24). The robust increase in food intake in
all three groups of mice after icv injection of U-50488 served as a
positive control for our experimental procedures (Fig. 3G).
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
PYY-(3–36), a potent Y2 and Y5 agonist with limited efficacy for rat Y1 receptors, is the most potent feeding stimulant after icv injection (14). In addition, hPP and bPP, which are effective Y4 and Y5 agonists, can evoke ingestive behavior (14). Because some Y2 and Y4 agonists fail to stimulate feeding behavior, the Y5 receptor has been considered a major feeding receptor (14, 25). As reported previously (21), we found that the orexigenic effect of PYY-(3–36) was significantly attenuated in Y5-/- mice compared with that in wild-type mice, although it was not abolished. Additionally, the Y5-preferring agonists, hPP and bPP, showed a tendency to induce reduced food intake in Y5-/- mice compared with that in wild-type mice. These data suggest that the Y5 receptor is indeed involved in feeding regulation.
Interestingly, although PYY-(3–36) has no agonist activity at rat Y1 receptors (14), we found that it has a significant affinity for mouse Y1 receptors (Ki = 35 nM). A similar affinity was reported for human Y1 receptors (26). These findings suggest that a fraction of PYY-(3–36)-induced feeding observed in Y5-/- mice might be evoked by agonism at the Y1 receptor. However, the similar orexigenic potency of PYY-(3–36) and NPY in Y5-/- mice cannot easily be explained by stimulation of the Y1 receptors, as the binding affinity of PYY-(3–36) at the Y1 receptor is about 40-fold less potent than that of NPY [0.84 nM NPY vs. 35 nM PYY-(3–36)]. The findings indicate that other subtypes of NPY receptor contribute to the feeding behavior elicited by PYY-(3–36) in Y5-/- mice. Based on the PYY-(3–36) binding affinities, a Y2-like receptor may be involved in feeding regulation. Consistent with a role for the Y2-like receptor are reports indicating that a Y2 agonist, NPY-(13–36), induced food intake or stimulated NPY-induced feeding (19, 27). However, a recent publication showed that icv NPY led to a similar increase in food intake in Y2-/- and wild-type mice (28). Thus, the typical Y2 receptor might not be involved in NPY-induced feeding. In mice, the affinity of the NPY ligands for y6 receptors has variously been reported as Y1-like, Y2-like, or Y4-like (26, 29, 30, 31). Thus, the y6 receptor might be a candidate for a Y2-like feeding receptor in mice. However, in rats and mice, PYY-(3–36) is the most potent feeding stimulant, even though rats (and primates) lack a functional y6 receptor (29, 30, 31), indicating that the y6 receptor is not an obligatory feeding receptor.
Significant food consumption induced by the Y4 and Y5 agonists, hPP and bPP, in Y5-/- mice also suggests the participation of other feeding receptors. The Y5-preferring agonists hPP, bPP and PYY-(3–36), have different efficacy for feeding stimulation despite their similar affinities for the Y1 and Y5 receptors. These findings demonstrate that their orexigenic effects could not be explained by the action of the Y1 and Y5 receptors, especially in Y5-/- mice. The lack of feeding stimulation by rPP in wild-type mice indicates that the typical Y4 receptor is not involved in feeding regulation. As mentioned previously, some reports showed that the y6 receptor has a Y4-like peptide affinity profile (26, 31). However, we found no evidence for binding of the PPs to the mouse y6 receptor, indicating that the y6 receptor does not mediate any of the actions of the PPs. Taken together with the highly significant orexigenic effect of PYY-(3–36) in Y5-/- mice, these findings suggest that novel subtypes of NPY receptors play an important role in feeding regulation.
Our data indicate that the Y1 receptor modulates the actions of other NPY receptors. This idea is supported by our finding that increased feeding induced by various peptides from the NPY family was reduced overall in Y1-/- mice compared with that in wild-type mice. Although we cannot completely exclude a weak direct action of these ligands at the Y1 receptor, the results indicate that feeding, through the action of the other NPY receptors, including the Y5 receptor, is modulated by the Y1 receptor. A potentially synergistic involvement of both the Y1 and Y5 receptors in mediating feeding behavior is consistent with a recent report showing that neurons positive for the Y5 receptor also express the Y1 receptor in the hypothalamus (32). It might be of interest to assess the relevance of two novel mechanisms, heterodimerization and heterologous receptor recruitment, in NPY receptor function (33, 34). Heterodimerization of NPY receptors might contribute to the unique pharmacology of a novel feeding receptor (33).
Finally, we have to consider the possibility that developmental compensation due to the inactivation of the Y1 or Y5 receptor may have affected the functioning of the remaining NPY receptors. For example, up-regulation of Y2, Y4, and/or y6 receptors could account for the residual feeding responses observed with PYY-(3–36) and PPs in Y5-/- mice. Experiments to evaluate receptor expression levels in the brains of NPY receptor-deficient mice are planned to further evaluate this model.
The feeding response evoked by NPY and its analogs in the wild-type, Y1-/-, and Y5-/- mice indicates the involvement of multiple NPY receptors, including a potentially novel feeding receptor(s). The Y1 receptor plays a critical role in NPY-induced feeding and may modulate the functioning of other NPY receptors. However, as the results presented here involve superphysiological doses of NPY ligands, additional studies are needed to characterize the role of NPY receptor subtypes under more physiologically relevant conditions. By combining the use of receptor-selective antagonists, various food intake models, and knockout mice, a clearer understanding of the role of NPY receptors will emerge.
|
Acknowledgments |
|---|
|
Footnotes |
|---|
Received August 17, 1999.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
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 |
