Neuropeptide Y receptors: how to get subtype selectivity

Pedragosa-Badia, Xavier; Stichel, Jan; Beck‐Sickinger, Annette G.

doi:10.3389/fendo.2013.00005

Cited by 137 publications

(135 citation statements)

References 123 publications

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“…Thus far, seven different Y receptors (Y1-Y8) have been reported in vertebrates [10-14], of which five (Y1, Y2, Y4, Y5, and y6) are cloned from mammals and four (hY1, hY2, hY4 and hY5) are proven functional in humans [15]. According to contemporary sequence alignment (current UniProtein sequences aligned in clustalO program), the Y receptors could be classified into two families, the Y1-Y4-Y6-Y8 (Y5) and the Y2-Y7 families; the first family is strongly expressed in neural tissue, and the second in visceral organs, especially kidney and intestine.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

Cell Physiol Biochem

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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.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2017

Cell Physiol Biochem

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“…Y6 is functional in rabbits and mice, but not in humans. Among these receptors, Y1 and Y5 are widely distributed throughout the brain, including the hypothalamus, and are thought to mediate primarily the orexigenic effects of NPY (Kamiji and Inui, 2007;Pedragosa-Badia et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Transient expression of neuropeptide W in postnatal mouse hypothalamus – A putative regulator of energy homeostasis

et al. 2015

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Neuropeptide B and W (NPB and NPW) are cognate peptide ligands for NPBWR1 (GPR7), a G protein-coupled receptor. In rodents, they have been implicated in the regulation of energy homeostasis, neuroendocrine/autonomic responses, and social interactions. Although localization of these peptides and their receptors in adult rodent brain has been well documented, their expression in mouse brain during development is unknown. Here we demonstrate the transient expression of NPW mRNA in the dorsomedial hypothalamus (DMH) of postnatal mouse brain and its co-localization with neuropeptide Y (NPY) mRNA. Neurons expressing both NPW and NPY mRNAs begin to emerge in the DMH at about postnatal day 0 (P-0) through P-3. Their expression is highest around P-14, declines after P-21, and by P-28 only a faint expression of NPW and NPY mRNA remains. In P-18 brains, we detected NPW neurons in the region spanning the subincertal nucleus (SubI), the lateral hypothalamic (LH) perifornical (PF) areas, and the DMH, where the highest expression of NPW mRNA was observed. The majority of these postnatal hypothalamic NPW neurons co-express NPY mRNA. A cross of NPW-iCre knock-in mice with a Cre-dependent tdTomato reporter line revealed that more than half of the reporter-positive neurons in the adult DMH, which mature from the transiently NPW-expressing neurons, are sensitive to peripherally administrated leptin. These data suggest that the DMH neurons that transiently co-express NPW and NPY in the peri-weaning period might play a role in regulating energy homeostasis during postnatal development.

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“…G protein-coupled receptors (GPCRs) 5 are the most prominent group of cell surface proteins. They are formed by seven transmembrane helices (TM) that are connected by intracellular and extracellular loops (ECL).…”

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confidence: 99%

“…These receptors are activated by the NPY family of peptide hormones, consisting of NPY, peptide YY (PYY), and pancreatic polypeptide (PP). NPY peptides and receptors form a multiligand/multireceptor system that plays a role in several physiological and pathological processes such as obesity and cancer (5). NPY peptides consist of 36 amino acids, are C-terminally amidated, and share high sequence identity.…”

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confidence: 99%

Pancreatic Polypeptide Is Recognized by Two Hydrophobic Domains of the Human Y4 Receptor Binding Pocket

Pedragosa-Badia

Sliwoski

Nguyen

et al. 2014

Journal of Biological Chemistry

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Background:The Y 4 R is involved in regulation of food intake and gastrointestinal transport. Results: Mutagenesis studies revealed several residues displaying a significant loss of potency for hPP. Conclusion: Tops of TM2, TM6, and TM7 interact with the hY 4 R native agonist hPP. Significance: Characterizing the structure of the Y 4 R binding pocket is crucial for the development of new anti-obesity drugs.

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Neuropeptide Y receptors: how to get subtype selectivity

Cited by 137 publications

References 123 publications

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

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

Transient expression of neuropeptide W in postnatal mouse hypothalamus – A putative regulator of energy homeostasis

Pancreatic Polypeptide Is Recognized by Two Hydrophobic Domains of the Human Y4 Receptor Binding Pocket

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