Visualization of Functional Neuropeptide Y Receptors in the Mouse Hippocampus and Neocortex Using [35S]GTPγS Binding

Heidi Elbrønd-Bek; Casper René Gøtzsche; Mette Skinbjerg; Ditte Z Christensen; Per Krener Plenge; David Paul Drucker Woldbye

doi:10.1007/s10989-015-9455-y

Visualization of Functional Neuropeptide Y Receptors in the Mouse Hippocampus and Neocortex Using [³⁵S]GTPγS Binding

Heidi Elbrønd-Bek, Casper René Gøtzsche, Mette Skinbjerg, Ditte Z Christensen, Per Krener Plenge, David Paul Drucker Woldbye

Neuropharm and Genetics

1 Citationer (Scopus)

Abstract

The peptide transmitter neuropeptide Y (NPY) has been implicated in a plethora of actions in the central nervous system, including the hippocampus and neocortex (NeoCx). Previous studies using traditional receptor autoradiography show that NPY receptor binding is altered under various pathophysiological conditions. However, these do not provide information about downstream signal transduction. To this means, agonist-stimulated [³⁵S]GTPγS binding has in recent years been introduced as a method for measuring receptor activation of intracellular G-proteins. In the present study, this method was further optimized to visualize the distribution of individual NPY receptor-mediated [³⁵S]GTPγS binding in the mouse hippocampus and NeoCx using the endogenous ligand NPY in combination with optimized concentrations of selective antagonists for Y1, Y2, and Y5 NPY receptors. Consistent with previous studies, Y1 receptor-mediated [³⁵S]GTPγS binding was mainly found in the dentate gyrus and NeoCx while Y2 receptor-mediated [³⁵S]GTPγS binding predominated in the hippocampal CA3 and CA1. Only very low levels of Y5 receptor-mediated [³⁵S]GTPγS binding appeared to be present in the hippocampus and NeoCx. Furthermore, the effect of NPY receptor antagonists per se was also studied. Both BIIE0246 and L-152,804 significantly attenuated the basal [³⁵S]GTPγS binding response, suggesting inverse agonism.

Originalsprog	Engelsk
Tidsskrift	International Journal of Peptide Research and Therapeutics
Vol/bind	21
Udgave nummer	3
Sider (fra-til)	269-278
Antal sider	10
ISSN	1573-3149
DOI	https://doi.org/10.1007/s10989-015-9455-y
Status	Udgivet - 27 sep. 2015

Adgang til dokumentet

10.1007/s10989-015-9455-y

Citationsformater

Visualization of Functional Neuropeptide Y Receptors in the Mouse Hippocampus and Neocortex Using [³⁵S]GTPγS Binding. / Elbrønd-Bek, Heidi; Gøtzsche, Casper René; Skinbjerg, Mette et al.

I: International Journal of Peptide Research and Therapeutics, Bind 21, Nr. 3, 27.09.2015, s. 269-278.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

@article{f983ecfd42d14de7b25cd8021186b2ef,

title = "Visualization of Functional Neuropeptide Y Receptors in the Mouse Hippocampus and Neocortex Using [35S]GTPγS Binding",

abstract = "The peptide transmitter neuropeptide Y (NPY) has been implicated in a plethora of actions in the central nervous system, including the hippocampus and neocortex (NeoCx). Previous studies using traditional receptor autoradiography show that NPY receptor binding is altered under various pathophysiological conditions. However, these do not provide information about downstream signal transduction. To this means, agonist-stimulated [35S]GTPγS binding has in recent years been introduced as a method for measuring receptor activation of intracellular G-proteins. In the present study, this method was further optimized to visualize the distribution of individual NPY receptor-mediated [35S]GTPγS binding in the mouse hippocampus and NeoCx using the endogenous ligand NPY in combination with optimized concentrations of selective antagonists for Y1, Y2, and Y5 NPY receptors. Consistent with previous studies, Y1 receptor-mediated [35S]GTPγS binding was mainly found in the dentate gyrus and NeoCx while Y2 receptor-mediated [35S]GTPγS binding predominated in the hippocampal CA3 and CA1. Only very low levels of Y5 receptor-mediated [35S]GTPγS binding appeared to be present in the hippocampus and NeoCx. Furthermore, the effect of NPY receptor antagonists per se was also studied. Both BIIE0246 and L-152,804 significantly attenuated the basal [35S]GTPγS binding response, suggesting inverse agonism.",

author = "Heidi Elbr{\o}nd-Bek and G{\o}tzsche, {Casper Ren{\'e}} and Mette Skinbjerg and Christensen, {Ditte Z} and Plenge, {Per Krener} and Woldbye, {David Paul Drucker}",

year = "2015",

month = sep,

day = "27",

doi = "10.1007/s10989-015-9455-y",

language = "English",

volume = "21",

pages = "269--278",

journal = "International Journal of Peptide Research and Therapeutics",

issn = "1573-3149",

publisher = "Springer",

number = "3",

}

TY - JOUR

T1 - Visualization of Functional Neuropeptide Y Receptors in the Mouse Hippocampus and Neocortex Using [35S]GTPγS Binding

AU - Elbrønd-Bek, Heidi

AU - Gøtzsche, Casper René

AU - Skinbjerg, Mette

AU - Christensen, Ditte Z

AU - Plenge, Per Krener

AU - Woldbye, David Paul Drucker

PY - 2015/9/27

Y1 - 2015/9/27

N2 - The peptide transmitter neuropeptide Y (NPY) has been implicated in a plethora of actions in the central nervous system, including the hippocampus and neocortex (NeoCx). Previous studies using traditional receptor autoradiography show that NPY receptor binding is altered under various pathophysiological conditions. However, these do not provide information about downstream signal transduction. To this means, agonist-stimulated [35S]GTPγS binding has in recent years been introduced as a method for measuring receptor activation of intracellular G-proteins. In the present study, this method was further optimized to visualize the distribution of individual NPY receptor-mediated [35S]GTPγS binding in the mouse hippocampus and NeoCx using the endogenous ligand NPY in combination with optimized concentrations of selective antagonists for Y1, Y2, and Y5 NPY receptors. Consistent with previous studies, Y1 receptor-mediated [35S]GTPγS binding was mainly found in the dentate gyrus and NeoCx while Y2 receptor-mediated [35S]GTPγS binding predominated in the hippocampal CA3 and CA1. Only very low levels of Y5 receptor-mediated [35S]GTPγS binding appeared to be present in the hippocampus and NeoCx. Furthermore, the effect of NPY receptor antagonists per se was also studied. Both BIIE0246 and L-152,804 significantly attenuated the basal [35S]GTPγS binding response, suggesting inverse agonism.

AB - The peptide transmitter neuropeptide Y (NPY) has been implicated in a plethora of actions in the central nervous system, including the hippocampus and neocortex (NeoCx). Previous studies using traditional receptor autoradiography show that NPY receptor binding is altered under various pathophysiological conditions. However, these do not provide information about downstream signal transduction. To this means, agonist-stimulated [35S]GTPγS binding has in recent years been introduced as a method for measuring receptor activation of intracellular G-proteins. In the present study, this method was further optimized to visualize the distribution of individual NPY receptor-mediated [35S]GTPγS binding in the mouse hippocampus and NeoCx using the endogenous ligand NPY in combination with optimized concentrations of selective antagonists for Y1, Y2, and Y5 NPY receptors. Consistent with previous studies, Y1 receptor-mediated [35S]GTPγS binding was mainly found in the dentate gyrus and NeoCx while Y2 receptor-mediated [35S]GTPγS binding predominated in the hippocampal CA3 and CA1. Only very low levels of Y5 receptor-mediated [35S]GTPγS binding appeared to be present in the hippocampus and NeoCx. Furthermore, the effect of NPY receptor antagonists per se was also studied. Both BIIE0246 and L-152,804 significantly attenuated the basal [35S]GTPγS binding response, suggesting inverse agonism.

U2 - 10.1007/s10989-015-9455-y

DO - 10.1007/s10989-015-9455-y

M3 - Journal article

SN - 1573-3149

VL - 21

SP - 269

EP - 278

JO - International Journal of Peptide Research and Therapeutics

JF - International Journal of Peptide Research and Therapeutics

IS - 3

ER -