Depressor Effect of Intrathecal Neuropeptide Y (NPY) Is Mediated by Y2 Subtype of NPY Receptors

1993 ◽  
Vol 21 (5) ◽  
pp. 720-724 ◽  
Author(s):  
Xiaoli Chen ◽  
Thomas C. Westfall
Keyword(s):  
Neuropeptide Y ◽  
Depressor Effect ◽  
Npy Receptors

Characterization of Neuropeptide Y ( NPY ) Receptors

1998 ◽  
Vol 1 (1) ◽  
Author(s):  
William Karbon ◽  
Julie Marasco ◽  
Clarence Hale
Keyword(s):  
Neuropeptide Y ◽  
Npy Receptors

scholarly journals A Promising Therapeutic Target for Metabolic Diseases: Neuropeptide Y Receptors in Humans

2017 ◽  
Vol 45 (1) ◽  
pp. 88-107 ◽  
Author(s):  
Min Yi ◽  
Hekai Li ◽  
Zhiye Wu ◽  
Jianyun Yan ◽  
Qicai Liu ◽  
...  
Keyword(s):  
Neuropeptide Y ◽  
Pancreatic Polypeptide ◽  
Metabolic Diseases ◽  
Peptide Yy ◽  
Cortical Excitability ◽  
Structural Characteristics ◽  
Mammalian Brain ◽  
Surface Receptors ◽  
Wide Range ◽  
Npy Receptors

Human neuropeptide Y (hNPY) is one of the most widely expressed neurotransmitters in the human central and peripheral nervous systems. It consists of 36 highly conserved amino acid residues, and was first isolated from the porcine hypothalamus in 1982. While it is the most recently discovered member of the pancreatic polypeptide family (which includes neuropeptide Y, gut-derived hormone peptide YY, and pancreatic polypeptide), NPY is the most abundant peptide found in the mammalian brain. In order to exert particular functions, NPY needs to bind to the NPY receptor to activate specific signaling pathways. NPY receptors belong to the class A or rhodopsin-like G-protein coupled receptor (GPCR) family and signal via cell-surface receptors. By binding to GPCRs, NPY plays a crucial role in various biological processes, including cortical excitability, stress response, food intake, circadian rhythms, and cardiovascular function. Abnormal regulation of NPY is involved in the development of a wide range of diseases, including obesity, hypertension, atherosclerosis, epilepsy, metabolic disorders, and many cancers. Thus far, five receptors have been cloned from mammals (Y1, Y2, Y4, Y5, and y6), but only four of these (hY1, hY2, hY4, and hY5) are functional in humans. In this review, we summarize the structural characteristics of human NPY receptors and their role in metabolic diseases.

Food intake regulation in rodents: Y5 or Y1 NPY receptors or both?

2000 ◽  
Vol 78 (2) ◽  
pp. 173-185 ◽  
Author(s):  
Jacques Duhault ◽  
Michèle Boulanger ◽  
Susana Chamorro ◽  
Jean A Boutin ◽  
Odile Della Zuana ◽  
...  
Keyword(s):  
Food Intake ◽  
Neuropeptide Y ◽  
Inhibitory Effect ◽  
Receptor Subtype ◽  
Pharmacological Characterization ◽  
Npy Receptor ◽  
Obesity Drugs ◽  
Npy Receptors

Neuropeptide Y (NPY), one of the most abundant peptides in rat and human brains, appears to act in the hypothalamus to stimulate feeding. It was first suggested that the NPY Y1 receptor (Y1R) was involved in feeding stimulated by NPY. More recently a novel NPY receptor subtype (Y5R) was identified in rat and human as the NPY feeding receptor subtype. There is, however, no absolute consensus since selective Y1R antagonists also antagonize NPY-induced hyperphagia. Nevertheless, new anti-obesity drugs may emerge from further pharmacological characterization of the NPY receptors and their antagonists. A large panel of Y1R and Y5R antagonists (such as CGP71683A, BIBO3304, BIBP3226, 1229U91, and SYNAPTIC and BANYU derivatives but also patentable in-house-synthesized compounds) have been evaluated through in vitro and in vivo tests in an attempt to establish a predictive relationship between the binding selectivity for human receptors, the potency in isolated organs assays, and the inhibitory effect on food intake in both normal and obese hyperphagic rodents. Although these results do not allow one to conclude on the implication of a single receptor subtype at the molecular level, this approach is crucial for the design of novel NPY receptor antagonists with potential use as anti-obesity drugs and for evaluation of their possible adverse peripheral side effects, such as hypotension.Key words: obesity, weight reduction, food intake, neuropeptide Y, rodents.

Specific neuropeptide Y binding sites in chicken brain

1991 ◽  
Vol 260 (6) ◽  
pp. E839-E845
Author(s):  
M. L. Adamo ◽  
R. L. Hazelwood
Keyword(s):  
Cerebral Cortex ◽  
Neuropeptide Y ◽  
Binding Sites ◽  
Brain Regions ◽  
Chicken Brain ◽  
High Affinity ◽  
Order Of Magnitude ◽  
Avian Pancreatic Polypeptide ◽  
Scatchard Plots ◽  
Npy Receptors

In the present study, 125I-labeled neuropeptide Y (NPY) binding to chicken brain regions was evaluated. Cerebellum and cerebral cortex membranes bound significantly more 125I-NPY specifically than did membranes from other brain regions. Scatchard plots of NPY binding to cerebellar membranes were curvilinear; the high-affinity component had an affinity (Kd) of 1.1 nM, with a receptor concentration (Ro) of 182 fmol/mg membrane protein. Scatchard plots of NPY binding to chicken cerebral cortex membranes were linear, with a Kd of 0.63 nM and Ro of 90 fmol/mg. Unlabeled avian pancreatic polypeptide (APP) inhibited 125I-NPY binding to cerebellar membranes with a constant at which 50% inhibition occurs of 0.5 nM but showed essentially no affinity for cerebral cortex NPY binding sites. As previously reported, 125I-APP bound to cerebellar membranes with a Kd of 0.365 nM and an Ro of 323 fmol/mg, and unlabeled NPY showed about one order of magnitude lower affinity than did unlabeled APP for 125I-APP binding sites. Pseudo-Hill coefficients for APP binding to cerebellar APP receptors and NPY binding to cerebellar NPY receptors were 0.9. In contrast, pseudo-Hill plots for APP competition for 125I-NPY binding were curvilinear. It is concluded that the chicken cerebellum contains distinct APP and NPY receptors, whereas cerebral cortex contains only NPY receptors. APP is capable of binding with high affinity to the cerebellar, but not the cortical, NPY receptor.

scholarly journals Autoreceptor-induced inhibition of neuropeptide Y release from PC-12 cells is mediated by Y2 receptors

1997 ◽  
Vol 273 (4) ◽  
pp. H1737-H1744 ◽  
Author(s):  
Xiaoli Chen ◽  
Debora A. Dimaggio ◽  
Song Ping Han ◽  
Thomas C. Westfall
Keyword(s):  
Neuropeptide Y ◽  
Peptide Yy ◽  
Dependent Manner ◽  
Inhibitory Effects ◽  
Ideal Model ◽  
Concentration Dependent Manner ◽  
Pc 12 Cells ◽  
Npy Receptor ◽  
Neuropeptide Y Release ◽  
Npy Receptors

Pheochromocytoma (PC)-12 cells express Y1, Y2, and Y3 neuropeptide Y (NPY) receptors when differentiated with nerve growth factor (NGF). The present work evaluated NGF-differentiated PC-12 cells as a model system to study modulation of NPY release by NPY autoreceptors. We demonstrated that both K+ and nicotine stimulated concomitant release of NPY and dopamine from differentiated PC-12 cells. We also showed in this study that NPY release from PC-12 cells was attenuated in a concentration-dependent manner by peptide YY (PYY)-(13—36), a selective agonist for the Y2 type of NPY receptors. This result demonstrated that NPY release could be modulated by NPY autoreceptors of the Y2 subtype. The inhibitory action of PYY-(13—36) may be mediated at least in part by inhibition of N-type Ca2+channels, because PYY-(13—36) could not produce further inhibitory effects in the presence of a maximum effective concentration of ω-conotoxin, an N-type Ca2+-channel blocker. The inhibition by PYY-(13—36) could be blocked by pretreatment of cells with pertussis toxin, suggesting that an inhibitory GTP-binding protein was involved. Furthermore, the function of NPY autoreceptors could be modulated by other receptors such as β-adrenergic and ATP receptors. The evoked release of NPY was also attenuated by ATP and adenosine, which have been shown to be colocalized and coreleased with NPY from sympathetic nerve terminals. These results suggest that PC-12 cells differentiated with NGF may be an ideal model to study regulatory mechanisms of NPY release and that autoreceptor-mediated regulation of NPY release appears to act through the Y2 subtype of the NPY receptor.

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