Neuropeptide Y Y1 receptors in the rat forebrain: Autoradiographic demonstration of [125I][Leu31,Pro34]-NPY binding sites and neurons expressing Y1 receptor mRNA

The neuroendocrine parvocellular CRH neurons in the paraventricular nucleus (PVN) of the hypothalamus are the main integrators of neural inputs that initiate hypothalamic-pituitary-adrenal (HPA) axis activation. Neuropeptide Y (NPY) expression is prominent within the PVN, and previous reports indicated that NPY stimulates CRH mRNA levels. The purpose of these studies was to examine the participation of NPY receptors in HPA axis activation and determine whether neuroendocrine CRH neurons express NPY receptor immunoreactivity. Infusion of 0.5 nmol NPY into the third ventricle increased plasma corticosterone levels in conscious rats, with the peak of hormone levels occurring 30 min after injection. This increase was prevented by pretreatment with the Y1 receptor antagonist BIBP3226. Immunohistochemistry showed that CRH-immunoreactive neurons coexpressed Y1 receptor immunoreactivity (Y1r-ir) in the PVN, and a majority of these neurons (88.8%) were neuroendocrine as determined by ip injections of FluoroGold. Bilateral infusion of the Y1/Y5 agonist, [leu31pro34]NPY (110 pmol), into the PVN increased c-Fos and phosphorylated cAMP response element-binding protein expression and elevated plasma corticosterone levels. Increased expression of c-Fos and phosphorylated cAMP response element-binding protein was observed in populations of CRH/Y1r-ir cells. The current findings present a comprehensive study of NPY Y1 receptor distribution and activation with respect to CRH neurons in the PVN. The expression of NPY Y1r-ir by neuroendocrine CRH cells suggests that alterations in NPY release and subsequent activation of NPY Y1 receptors plays an important role in the regulation of the HPA.

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Different binding sites for the neuropeptide Y Y1 antagonists 1229U91 and J-104870 on human Y1 receptors

Peptides ◽

10.1016/s0196-9781(01)00350-3 ◽

2001 ◽

Vol 22 (3) ◽

pp. 405-413 ◽

Cited By ~ 25

Author(s):

Tetsuya Kannoa ◽

Akio Kanatani ◽

Sabina L.C. Keen ◽

Sachie Arai-Otsuki ◽

Yuji Haga ◽

...

Keyword(s):

Neuropeptide Y ◽

Binding Sites ◽

Y1 Receptors

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Chronic Administration of Glucocorticoids Directly Upregulates Prepro-Neuropeptide Y and Y1-Receptor mRNA Levels in the Arcuate Nucleus of the Rat

Journal of Neuroendocrinology ◽

10.1111/j.1365-2826.1994.tb00566.x ◽

1994 ◽

Vol 6 (2) ◽

pp. 153-159 ◽

Cited By ~ 58

Author(s):

Philip J. Larsen ◽

David S. Jessop ◽

Hardial S. Chowdrey ◽

Stafford L. Lightman ◽

Jens D. Mikkelsen

Keyword(s):

Neuropeptide Y ◽

Arcuate Nucleus ◽

Chronic Administration ◽

Mrna Levels ◽

Y1 Receptor ◽

Receptor Mrna

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Modeling the G-protein-coupled neuropeptide Y Y1 receptor agonist and antagonist binding sites

Protein Engineering Design and Selection ◽

10.1093/protein/10.2.109 ◽

1997 ◽

Vol 10 (2) ◽

pp. 109-117 ◽

Cited By ~ 47

Author(s):

P. Du ◽

J. A. Salon ◽

J. A. Tamm ◽

C. Hou ◽

W. Cui ◽

...

Keyword(s):

Neuropeptide Y ◽

G Protein ◽

Binding Sites ◽

Receptor Agonist ◽

Y1 Receptor ◽

Agonist And Antagonist ◽

Antagonist Binding ◽

G Protein Coupled

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Role of G-protein βγ subunits in the augmentation of P2Y2 (P2U) receptor-stimulated responses by neuropeptide Y Y1 Gi/o-coupled receptors

Biochemical Journal ◽

10.1042/bj3280153 ◽

1997 ◽

Vol 328 (1) ◽

pp. 153-158 ◽

Cited By ~ 36

Author(s):

A. Lisa SELBIE ◽

V. Natalie KING ◽

M. John DICKENSON ◽

J. Stephen HILL

Keyword(s):

Neuropeptide Y ◽

G Protein ◽

Binding Proteins ◽

Synergistic Interaction ◽

Y1 Receptor ◽

Gtp Binding ◽

Adenosine A1 ◽

Y1 Receptors ◽

Stimulation Of

Neuropeptide Y (NPY) significantly potentiates the constrictor actions of noradrenaline and ATP on blood vessels via a pertussis toxin (PTX)-sensitive mechanism involving Gi/o (αβγ) protein subunits (Gi/o, GTP-binding proteins sensitive to PTX). In Chinese hamster ovary K1 (CHO K1) cells expressing specific receptors for these neurotransmitters, stimulation of Gi/o protein-coupled receptors for NPY and other neurotransmitters can augment the Gq/11-coupled (Gq/11, GTP-binding proteins insensitive to PTX) α1B adrenoceptor- or ATP receptor-induced arachidonic acid (AA) release and inositol phosphate (IP) production (early events which may precede vasoconstriction). In this study, we have assessed the role of Gβγ subunits in the synergistic interaction between Gi/o- (NPY Y1, 5-hydroxytryptamine 5-HT1B, adenosine A1) and Gq/11- [ATP P2Y2 (P2U)]-coupled receptors on AA release by using the specific abilities of regions of the β-adrenergic receptor kinase (βARK1 residues 495-689) and the transducin α subunit to associate with G-protein βγ subunit dimers and to act as Gβγ subunit scavengers. Transient expression of βARK1(495-689) in CHO K1 cells heterologously expressing NPY Y1 receptors had no significant effect on the PTX-insensitive ability of ATP to stimulate AA release. Stimulation of NPY Y1 receptors (as well as the endogenous 5-hydroxytryptamine 5-HT1B receptor and the transiently expressed human adenosine A1 receptor) resulted in a PTX-sensitive augmentation of ATP-stimulated AA release, which was inhibited by expression of both Gβγ subunit scavengers. Expression of βARK1(495-689) similarly inhibited NPY Y1 receptor augmentation of ATP-stimulated IP production (a measure of phospholipase C activity), a step thought to precede the NPY Y1 receptor-augmented protein kinase C-dependent AA release previously observed in these cells. These experiments demonstrate that Gβγ subunits, as inhibited by two different Gβγ scavengers, significantly contribute to the synergistic interaction between NPY Y1 Gi/o- and Gq/11-coupled receptor activity, and are required for the augmentation of IP production and AA release observed in this model cell system.

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Stress-induced mesenteric vasoconstriction in rats is mediated by neuropeptide Y Y1 receptors

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1996.270.2.h796 ◽

1996 ◽

Vol 270 (2) ◽

pp. H796-H800 ◽

Cited By ~ 4

Author(s):

Z. Zukowska-Grojec ◽

E. K. Dayao ◽

E. Karwatowska-Prokopczuk ◽

G. J. Hauser ◽

H. N. Doods

Keyword(s):

Neuropeptide Y ◽

Vascular Resistance ◽

Cold Water ◽

Pressor Response ◽

Physiological Role ◽

Y1 Receptor ◽

Y1 Receptors ◽

Mesenteric Artery Blood Flow ◽

Mesenteric Vascular Resistance

The physiological role of neuropeptide Y (NPY), a sympathetic cotransmitter and vasoconstrictor, has not been determined yet. We used a specific nonpeptide antagonist to the NPY Y1 receptor [BIBP-3226; (R)-N2-(diphenacetyl)-N-[(4-hydroxyphenyl) methyl]-D-arginineamide] to study the involvement of NPY in stress-induced vasoconstriction in the mesenteric bed. In rats subjected to cold water stress (COLD), plasma NPY immunoreactivity levels increased progressively from 0.15 +/- 0.01 to 0.32 +/- 0.05 pmol/ml and remained elevated during recovery. Administration of BIBP-3226 (3 mg.kg-1.h-1 infusion) tended to decrease the stress-induced pressor response and significantly attenuated the post-COLD elevation of blood pressure. The COLD-induced fall in the superior mesenteric artery blood flow and the increase of up to 300% in the mesenteric vascular resistance were either reduced or eliminated by BIBP-3226. Conversely, the Y1 antagonist had no effect on the COLD-induced tachycardia. This study provides the first evidence of the physiological role of NPY. The peptide is released during stress and increases mesenteric vascular resistance via activation of its Y1 receptors. Specific Y1-receptor antagonists may therefore be of potential benefit in prevention or treatment of stress-induced vasospasm.

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