[125I]‐GR231118: a high affinity radioligand to investigate neuropeptide Y Y1 and Y4 receptors

Dumont, Yvan; Quirion, Rémi

doi:10.1038/sj.bjp.0702983

Cited by 44 publications

(35 citation statements)

References 76 publications

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“…The presence of Y 2 receptors has already been demonstrated in the subfornical organ (Dumont et al 1996), whereas the Y 4 and Y 5 subtypes are apparently absent in this region of the rat brain (Dumont et al 2000b). In the area postrema, the presence of Y 1 (Dumont et al 2000c), Y 2 (Dumont et al 2000a), Y 4 (Dumont et al 2000c), and Y 5 (Dumont et al 2004b) receptors has been reported in the rat brain. Accordingly, if PYY(3-36) and hPP induce their anorexic effects by activating a common receptor subtype, it cannot be of the Y 1 , Y 2 , or Y 4 classes.…”

Section: Discussionmentioning

confidence: 94%

Distribution of Peripherally Injected Peptide YY ([125I] PYY (3–36)) and Pancreatic Polypeptide ([125I] hPP) in the CNS: Enrichment in the Area Postrema

et al. 2007

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The mechanism by which blood-borne peptide YY (3-36) (PYY(3-36)) and pancreatic polypeptide (PP) inhibit food intake is not clear and could implicate peripheral (vagal afferent pathways) and/or central (direct action on specific brain nuclei) mechanisms. To identify the primary brain structure(s) that could be activated after a peripheral injection of neuropeptide Y-related peptides, we investigated the distribution of radioactive materials using whole body autoradiography and coronal brain sections. Rats were injected with [125I] porcine (p) PYY(3-36) (i.p., 10 microCi) and killed after 30 min, 1, 2, or 4 h. After i.p. administration, significant amounts of radioactive materials were rapidly (<30 min) detected in the blood circulation and various tissues including the kidneys, liver, lung, heart, bone marrow, gastrointestinal tract, and thyroid gland, whereas in the brain, low but significant amounts of radioactive materials were detected at the level of the area postrema. Next, we investigated the distribution of radioactive labeling in the brain after i.v. injections of [125I]pPYY(3-36) (Y2 and Y5 subtypes), [125I] human (h) PP (Y4 and Y5 receptors), and [125I][Leu(31), Pro(34)] pPYY (Y1, Y4 and Y5 classes) in the rat brain. Fifteen minutes post injection, autoradiograms revealed positive signals only in the area postrema after the injection of [125I]-hPP and [125I][Leu(31), Pro(34)]pPYY. Whereas the presence of [125I]pPYY(3-36)-related labeling was detected in the area postrema, subfornical organ, and median eminence. In all other brain structures, including all hypothalamic nuclei and other circumventricular organs, near background level signals were detected. These data suggest that the inhibition of food intake observed after peripheral injections of pPYY(3-36) and hPP could involve receptor activation preferentially located at the level of the area postrema, a structure well-known to be involved in the modulation of food intake.

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Section: Discussionmentioning

confidence: 94%

Distribution of Peripherally Injected Peptide YY ([125I] PYY (3–36)) and Pancreatic Polypeptide ([125I] hPP) in the CNS: Enrichment in the Area Postrema

et al. 2007

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“…The Y4 receptor mRNA appears to be most abundant in the paraventricular nucleus and ARC (52,55,56) and may regulate other functions. This dose was thus increased to 24 g and the experiment repeated.…”

Section: Discussionmentioning

confidence: 97%

Y2 Receptor-Selective Agonist Delays the Estrogen-Induced Luteinizing Hormone Surge in Ovariectomized Ewes, but Y1-Receptor-Selective Agonist Stimulates Voluntary Food Intake

Clarke¹,

Backholer²,

Tilbrook³

2005

Endocrinology

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Neuropeptide Y (NPY) plays a major role in the regulation of food intake, regulation of homeostasis, and neuroendocrine function. We have previously shown that third ventricular infusion of this peptide delays the estradiol benzoate-induced surge in LH secretion in ovariectomized ewes. To determine the receptor subtype that transmits this effect, we have now used the same model to infuse a Y1 receptor agonist [NPY Leu31 Pro34], a Y2 receptor agonist (PYY3-36), and a Y4 receptor agonist (pancreatic polypeptide). We monitored the surges in animals given these agonists or artificial cerebrospinal fluid by measuring plasma LH levels, and we also measured daily voluntary food intake (VFI). A low (7 microg/h) dose of Y2 agonist delayed the surge but did not affect VFI, whereas a higher dose (14 microg/h) stimulated VFI. A dose of 18 microg/h of the Y1 agonist did not affect surge generation but also stimulated VFI. A dose of 24 microg/h of Y4 agonist affected neither surge generation nor VFI. These specificities are different from those reported for the rat and human (in which a Y2 agonist causes reduction in VFI). We conclude that, in sheep, the negative regulation of the reproductive axis by NPY and Y-receptor agonists is effected via the Y2 receptors, whereas the orexigenic effects are most likely effected via the Y1 receptors.

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“…Quantitative receptor autoradiography for NPY-receptor subtypes Y1 and Y2 was performed as previously described (27,28 Statistics. For all data that followed criteria of parametric tests, analysis of variance was used and followed, when appropriate, by Tukey honest significant difference post hoc test.…”

Section: Punished Drinking Testmentioning

confidence: 99%

Behavioral insensitivity to restraint stress, absent fear suppression of behavior and impaired spatial learning in transgenic rats with hippocampal neuropeptide Y overexpression

Thorsell

Michalkiewicz

Dumont

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

285

192

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Exogenous neuropeptide Y (NPY) reduces experimental anxiety in a wide range of animal models. The generation of an NPYtransgenic rat has provided a unique model to examine the role of endogenous NPY in control of stress and anxiety-related behaviors using paradigms previously used by pharmacological studies. Locomotor activity and baseline behavior on the elevated plus maze were normal in transgenic subjects. Two robust phenotypic traits were observed. (i) Transgenic subjects showed a markedly attenuated sensitivity to behavioral consequences of stress, in that they were insensitive to the normal anxiogenic-like effect of restraint stress on the elevated plus maze and displayed absent fear suppression of behavior in a punished drinking test. (ii) A selective impairment of spatial memory acquisition was found in the Morris water maze. Control experiments suggest these traits to be independent. These phenotypic traits were accompanied by an overexpression of prepro-NPY mRNA and NPY peptide and decreased NPY-Y1 binding within the hippocampus, a brain structure implicated both in memory processing and stress responses. Data obtained using this unique model support and extend a previously postulated anti-stress action of NPY and provide novel evidence for a role of NPY in learning and memory.anxiety ͉ amygdala N europeptide Y (NPY) (1) is highly expressed in the mammalian brain. Its pharmacological administration into the central nervous system reduces experimental anxiety in a wide range of animal models (2-5), but its involvement in memory function is less clear. NPY receptors cloned to date all belong to the superfamily of G protein-coupled receptors but differ in their ligand affinity profiles. The NPY-Y1 receptor (6-8) requires the intact NPY sequence for recognition and activation, and seems to be the subtype mediating anti-anxiety actions of NPY (3-5, 9, 10). The Y2 receptor subtype is also activated by C-terminal fragments of NPY, such as NPY 13-36 (11). The highest number of NPY-binding sites, predominantly of the Y2 subtype, is found within the hippocampus. Activation of Y2 receptors within this structure has been shown to suppress hippocampal glutamatergic transmission through presynaptic mechanisms (12, 13), but the behavioral consequences of Y2 signaling in this area are unclear.In agreement with anti-stress effects observed following central administration of NPY, a role for endogenous NPY in control of stress and anxiety-related behaviors is suggested by several findings. Acute physical restraint, which promotes experimental anxiety (14), suppresses NPY mRNA and peptide levels within the amygdala and cortex. In contrast, repeated exposure to the same stressor once daily for 10 days leads to a complete behavioral and endocrine habituation, accompanied by an up-regulation of amygdala NPY expression (15). We have therefore proposed that an up-regulation of NPY expression may contribute to the behavioral adaptation to stress. This extends a hypothesis that NPY may act to ''buffer'' behavioral effects of st...

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[¹²⁵I]‐GR231118: a high affinity radioligand to investigate neuropeptide Y Y₁ and Y₄ receptors

Cited by 44 publications

References 76 publications

Distribution of Peripherally Injected Peptide YY ([125I] PYY (3–36)) and Pancreatic Polypeptide ([125I] hPP) in the CNS: Enrichment in the Area Postrema

Distribution of Peripherally Injected Peptide YY ([125I] PYY (3–36)) and Pancreatic Polypeptide ([125I] hPP) in the CNS: Enrichment in the Area Postrema

Y2 Receptor-Selective Agonist Delays the Estrogen-Induced Luteinizing Hormone Surge in Ovariectomized Ewes, but Y1-Receptor-Selective Agonist Stimulates Voluntary Food Intake

Behavioral insensitivity to restraint stress, absent fear suppression of behavior and impaired spatial learning in transgenic rats with hippocampal neuropeptide Y overexpression

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