Overexpression of orphan receptor GPR61 increases cAMP levels upon forskolin stimulation in HEK293 cells: in vitro and in silico validation of 5-(nonyloxy)tryptamine as a low-affinity inverse agonist

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@article{72fcde63d73044b795929b340b578911,
title = "Overexpression of orphan receptor GPR61 increases cAMP levels upon forskolin stimulation in HEK293 cells: in vitro and in silico validation of 5-(nonyloxy)tryptamine as a low-affinity inverse agonist",
abstract = "GPR61 is an orphan receptor that belongs to Class A of G-protein-coupled receptors. It has been reported that GPR61 has a constitutive activity and couples to Gαs. In the present study, we characterized GPR61 function and ligand binding by experimental and molecular docking studies. We demonstrated that heterologous expression of GPR61 in HEK293 cells enhanced the cAMP synthesis response to forskolin, whereas the basal cAMP synthesis was unaffected. 5-(Nonyloxy)tryptamine inhibited forskolin-stimulated cAMP production in GPR61-expressing HEK293 cells. These studies highlight that the intrinsic activity of this receptor is only measurable following its synergy with Gαs.",
keywords = "Constitutive activity, GPR61, Inverse agonist, Molecular modeling, Proteins, Receptor",
author = "Pawel Kozielewicz and Gillian Grafton and Sajkowska-Kozielewicz, {Joanna J} and Barnes, {Nicholas M}",
note = "{\textcopyright} 2019 S. Karger AG, Basel.",
year = "2019",
month = jul,
day = "26",
doi = "10.1159/000501926",
language = "English",
journal = "Pharmacology",
issn = "0031-7012",
publisher = "Karger",

}

RIS

TY - JOUR

T1 - Overexpression of orphan receptor GPR61 increases cAMP levels upon forskolin stimulation in HEK293 cells

T2 - in vitro and in silico validation of 5-(nonyloxy)tryptamine as a low-affinity inverse agonist

AU - Kozielewicz, Pawel

AU - Grafton, Gillian

AU - Sajkowska-Kozielewicz, Joanna J

AU - Barnes, Nicholas M

N1 - © 2019 S. Karger AG, Basel.

PY - 2019/7/26

Y1 - 2019/7/26

N2 - GPR61 is an orphan receptor that belongs to Class A of G-protein-coupled receptors. It has been reported that GPR61 has a constitutive activity and couples to Gαs. In the present study, we characterized GPR61 function and ligand binding by experimental and molecular docking studies. We demonstrated that heterologous expression of GPR61 in HEK293 cells enhanced the cAMP synthesis response to forskolin, whereas the basal cAMP synthesis was unaffected. 5-(Nonyloxy)tryptamine inhibited forskolin-stimulated cAMP production in GPR61-expressing HEK293 cells. These studies highlight that the intrinsic activity of this receptor is only measurable following its synergy with Gαs.

AB - GPR61 is an orphan receptor that belongs to Class A of G-protein-coupled receptors. It has been reported that GPR61 has a constitutive activity and couples to Gαs. In the present study, we characterized GPR61 function and ligand binding by experimental and molecular docking studies. We demonstrated that heterologous expression of GPR61 in HEK293 cells enhanced the cAMP synthesis response to forskolin, whereas the basal cAMP synthesis was unaffected. 5-(Nonyloxy)tryptamine inhibited forskolin-stimulated cAMP production in GPR61-expressing HEK293 cells. These studies highlight that the intrinsic activity of this receptor is only measurable following its synergy with Gαs.

KW - Constitutive activity

KW - GPR61

KW - Inverse agonist

KW - Molecular modeling

KW - Proteins

KW - Receptor

UR - http://www.scopus.com/inward/record.url?scp=85070762814&partnerID=8YFLogxK

U2 - 10.1159/000501926

DO - 10.1159/000501926

M3 - Article

C2 - 31352450

JO - Pharmacology

JF - Pharmacology

SN - 0031-7012

ER -