Expression Cloning and Pharmacological Characterization of a Human Hippocampal Neuropeptide Y/Peptide YY Y2 Receptor Subtype

Gerald, Christophe; Walker, Mary W.; Vaysse, Pierre J.‐J.; He, Chaogang; Branchek, Theresa A.; Weinshank, Richard L.

doi:10.1074/jbc.270.45.26758

Cited by 258 publications

(121 citation statements)

References 44 publications

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“…The library was plated on agar plates (ampicillin selection) in 584 primary pools of ϳ4,500 independent clones. Preparation and transfection of library pool DNA were carried out as described (23). Forty-eight h after transfection, the galanin binding assay was carried out with 1 nM 125 I-porcine galanin ( 125 IpGAL; specific activity ϳ2200 Ci/mmol; NEN Life Science Products) in 20 mM HEPES-NaOH, pH 7.4, containing 1.26 mM CaCl 2 , 0.81 mM MgSO 4 , 0.44 mM KH 2 PO 4 , 5.4 mM KCl, 10 mM NaCl, 0.1% bovine serum albumin, and 0.1% bacitracin for 1 h at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Expression Cloning of a Rat Hypothalamic Galanin Receptor Coupled to Phosphoinositide Turnover

Smith

Forray

Walker

et al. 1997

Journal of Biological Chemistry

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The neuropeptide galanin is widely distributed throughout the central and peripheral nervous systems and participates in the regulation of processes such as nociception, cognition, feeding behavior, and insulin secretion. Multiple galanin receptors are predicted to underlie its physiological effects. We now report the isolation by expression cloning of a rat galanin receptor cDNA distinct from GALR1. The receptor, termed GALR2, was isolated from a rat hypothalamus cDNA library using a 125 I-porcine galanin (

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Section: Methodsmentioning

confidence: 99%

Expression Cloning of a Rat Hypothalamic Galanin Receptor Coupled to Phosphoinositide Turnover

Smith

Forray

Walker

et al. 1997

Journal of Biological Chemistry

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189

200

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“…A low-phase Fouriertransform filter was used to reduce high-frequency noise. The ellipticity was expressed as mean-residue molar ellipticity [Q] R in deg´cm 2´d mol 21 . The secondary structure components were calculated by the secondary structure estimation Program (JASCO), based on the reference spectra of Yang [42].…”

Section: Spectroscopymentioning

confidence: 99%

Novel analogues of neuropeptide Y with a preference for the Y₁‐receptor

Söll

Dinger

Lundell

et al. 2001

European Journal of Biochemistry

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In contrast, cyclo S±S [Cys20,Cys24]pNPY was found to be a highly selective ligand at the Y 2 -receptor, binding only threefold less efficiently than NPY. Analogues containing variations of positions 31 and 32 showed highly reduced affinity to the Y 1 -receptor, while binding to the Y 5 -receptor was affected less. Inhibition of cAMP-accumulation of selected peptides with replacements within position 20±23 of NPY showed preserved agonistic properties. The NPY analogues tested give insights into ligand±receptor interaction of NPY at the Y 1 -, Y 2 -and Y 5 -receptor and contribute to our understanding of subtype selectivity. Furthermore, the Y 1 -receptor-preferring peptides are novel tools that will provide insight into the physiological role of the Y 1 -receptor.Keywords: food intake; neuropeptides; NPY; selective ligands; structure±affinity relationship.Obesity, food intake and energy homeostasis are key areas of growing importance because obesity is beginning to replace malnutrition and infectious diseases as the most significant contributor to ill health in the developed world [1]. Neuropeptide Y (NPY) is one of the most important effector molecules of leptin: it is a key molecule in the regulation of food intake, it acts via several different receptor subtypes and elicits several physiological effects. Profound effects on stimulation of food intake, secretion of luteinizing and growth hormone, and insulin release suggest an important role for NPY in the pathophysiology of obesity and diabetes [2±5]. A wide range of other effects of NPY have been reported, such as potent vasoconstriction [6], facilitation of learning and memory [7], modulation of locomotor behaviours [8], induction of hypothermia [9,10], inhibition of sexual behaviour [11], shifts in circadian rhythms [12], modulation of cardiorespiratory parameters[13], anxiolytic potency [14] and inhibition of alcohol consumption and resistance [15].NPY is a 36-amino acid peptide amide belonging to the family of pancreatic polypeptides that includes also pancreatic polypeptide (PP) and peptide YY; it was first isolated from pig brain in 1982 [16].NPY is widely distributed within the central nervous system and in the periphery. [25,26]. A putative Y 3 -receptor has been described only pharmacologically and no specific agonists or antagonists are known [27]. All receptors belong to the G-protein coupled receptor superfamily [28]. The correlation of a certain receptor subtype to a distinct physiological effect is not yet fully understood. Recent studies even suggest that different receptor subtypes redundantly mediate identical actions in a given system, as has been shown for the Y 1 -and Y 5 -receptor in the regulation of food intake [3]. Findings that deficiencies in either the Y 1 -or the Y 5 -receptors do not significantly impair the normal feeding response to fasting or NPY stimulation, strongly indicate that both Y receptors are involved in appetite regulation by NPY [29,30]. Selective receptor agonists or antagonists are useful tools with which to stu...

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“…PP binds primarily to the Y4 receptor 7 and PYY 3À36 binds predominantly to the Y2 receptor. 8 In addition to their central actions, PP and PYY may also inhibit food intake through a reduction in gut motility. 9,10 There is evidence that co-administration of appetiterelated peptides may inhibit feeding synergistically.…”

Section: Introductionmentioning

confidence: 99%

No evidence of an additive inhibitory feeding effect following PP and PYY3−36 administration

et al. 2008

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Pancreatic polypeptide (PP) and peptide YY (PYY) are released by the gut in response to nutrients and inhibit food intake in rodents and humans. We hypothesized that PP and PYY 3À36 would inhibit feeding additively. Fasted male C57BL/6 mice were injected intraperitoneally with saline, PP, PYY 3À36 or PP þ PYY 3À36 (n ¼ 7-10). Food intake at 1 h was significantly inhibited by 6 nmol kg À1 PP and by 6 nmol kg À1 PYY 3-36 (Po0.05) but not significantly following 3 nmol kg À1 PP þ 3 nmol kg À1 PYY 3À36 . In a higher dose study 30 nmol kg À1 PP, 30 nmol kg À1 PYY 3À36 and 30 nmol kg À1 PP þ 30 nmol kg À1 PYY 3À36 all inhibited 1 h food intake compared with saline (Po0.05) but there was no significant difference in the food intake of the combined group compared with either hormone individually. Subsequently, 16 fasted lean healthy human volunteers (6 men and 10 women) received, in random order, 90 min intravenous infusions of saline, 4 pmol kg À1 min À1 PP, 0.4 pmol kg À1 min À1 PYY 3À36 and 4 pmol kg À1 min À1 PP þ 0.4 pmol kg À1 min À1 PYY 3À36 . A pasta lunch was served 60 min following infusion. There was no evidence of a greater decrease in food intake with the combined PP þ PYY 3À36 treatment (buffet meal energy intake (KJ): saline 2633 ± 204, PP þ PYY 2693 ± 254, PP 2367 ± 199, PYY 2511 ± 196). These results suggest that PP and PYY 3À36 do not inhibit feeding additively in rodents or humans.

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Expression Cloning and Pharmacological Characterization of a Human Hippocampal Neuropeptide Y/Peptide YY Y2 Receptor Subtype

Cited by 258 publications

References 44 publications

Expression Cloning of a Rat Hypothalamic Galanin Receptor Coupled to Phosphoinositide Turnover

Expression Cloning of a Rat Hypothalamic Galanin Receptor Coupled to Phosphoinositide Turnover

Novel analogues of neuropeptide Y with a preference for the Y₁‐receptor

No evidence of an additive inhibitory feeding effect following PP and PYY3−36 administration

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Expression Cloning and Pharmacological Characterization of a Human Hippocampal Neuropeptide Y/Peptide YY Y2 Receptor Subtype

Cited by 258 publications

References 44 publications

Expression Cloning of a Rat Hypothalamic Galanin Receptor Coupled to Phosphoinositide Turnover

Expression Cloning of a Rat Hypothalamic Galanin Receptor Coupled to Phosphoinositide Turnover

Novel analogues of neuropeptide Y with a preference for the Y1‐receptor

No evidence of an additive inhibitory feeding effect following PP and PYY3−36 administration

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Novel analogues of neuropeptide Y with a preference for the Y₁‐receptor