Functional characteristics of the naked mole rat μ-opioid receptor.

While humans and most animals respond to µ-opioid receptor (MOR) agonists with analgesia and decreased aggression, in the naked mole rat (NMR) opioids induce hyperalgesia and severe aggression. Single nucleotide polymorphisms in the human mu-opioid receptor gene (OPRM1) can underlie altered behavior...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Melanie Busch-Dienstfertig, Clarisse A Roth, Christoph Stein
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2013
Materias:
R
Q
Acceso en línea:https://doaj.org/article/641437eb37c945e2a1e871e5de2bb1fd
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:641437eb37c945e2a1e871e5de2bb1fd
record_format dspace
spelling oai:doaj.org-article:641437eb37c945e2a1e871e5de2bb1fd2021-11-18T08:44:30ZFunctional characteristics of the naked mole rat μ-opioid receptor.1932-620310.1371/journal.pone.0079121https://doaj.org/article/641437eb37c945e2a1e871e5de2bb1fd2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24312175/?tool=EBIhttps://doaj.org/toc/1932-6203While humans and most animals respond to µ-opioid receptor (MOR) agonists with analgesia and decreased aggression, in the naked mole rat (NMR) opioids induce hyperalgesia and severe aggression. Single nucleotide polymorphisms in the human mu-opioid receptor gene (OPRM1) can underlie altered behavioral responses to opioids. Therefore, we hypothesized that the primary structure of the NMR MOR may differ from other species. Sequencing of the NMR oprm1 revealed strong homology to other mammals, but exposed three unique amino acids that might affect receptor-ligand interactions. The NMR and rat oprm1 sequences were cloned into mammalian expression vectors and transfected into HEK293 cells. Radioligand binding and 3'-5'-cyclic adenosine monophosphate (cAMP) enzyme immunoassays were used to compare opioid binding and opioid-mediated cAMP inhibition. At normalized opioid receptor protein levels we detected significantly lower [3H]DAMGO binding to NMR compared to rat MOR, but no significant difference in DAMGO-induced cAMP inhibition. Strong DAMGO-induced MOR internalization was detectable using radioligand binding and confocal imaging in HEK293 cells expressing rat or NMR receptor, while morphine showed weak or no effects. In summary, we found minor functional differences between rat and NMR MOR suggesting that other differences e.g. in anatomical distribution of MOR underlie the NMR's extreme reaction to opioids.Melanie Busch-DienstfertigClarisse A RothChristoph SteinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e79121 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Melanie Busch-Dienstfertig
Clarisse A Roth
Christoph Stein
Functional characteristics of the naked mole rat μ-opioid receptor.
description While humans and most animals respond to µ-opioid receptor (MOR) agonists with analgesia and decreased aggression, in the naked mole rat (NMR) opioids induce hyperalgesia and severe aggression. Single nucleotide polymorphisms in the human mu-opioid receptor gene (OPRM1) can underlie altered behavioral responses to opioids. Therefore, we hypothesized that the primary structure of the NMR MOR may differ from other species. Sequencing of the NMR oprm1 revealed strong homology to other mammals, but exposed three unique amino acids that might affect receptor-ligand interactions. The NMR and rat oprm1 sequences were cloned into mammalian expression vectors and transfected into HEK293 cells. Radioligand binding and 3'-5'-cyclic adenosine monophosphate (cAMP) enzyme immunoassays were used to compare opioid binding and opioid-mediated cAMP inhibition. At normalized opioid receptor protein levels we detected significantly lower [3H]DAMGO binding to NMR compared to rat MOR, but no significant difference in DAMGO-induced cAMP inhibition. Strong DAMGO-induced MOR internalization was detectable using radioligand binding and confocal imaging in HEK293 cells expressing rat or NMR receptor, while morphine showed weak or no effects. In summary, we found minor functional differences between rat and NMR MOR suggesting that other differences e.g. in anatomical distribution of MOR underlie the NMR's extreme reaction to opioids.
format article
author Melanie Busch-Dienstfertig
Clarisse A Roth
Christoph Stein
author_facet Melanie Busch-Dienstfertig
Clarisse A Roth
Christoph Stein
author_sort Melanie Busch-Dienstfertig
title Functional characteristics of the naked mole rat μ-opioid receptor.
title_short Functional characteristics of the naked mole rat μ-opioid receptor.
title_full Functional characteristics of the naked mole rat μ-opioid receptor.
title_fullStr Functional characteristics of the naked mole rat μ-opioid receptor.
title_full_unstemmed Functional characteristics of the naked mole rat μ-opioid receptor.
title_sort functional characteristics of the naked mole rat μ-opioid receptor.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/641437eb37c945e2a1e871e5de2bb1fd
work_keys_str_mv AT melaniebuschdienstfertig functionalcharacteristicsofthenakedmoleratmopioidreceptor
AT clarissearoth functionalcharacteristicsofthenakedmoleratmopioidreceptor
AT christophstein functionalcharacteristicsofthenakedmoleratmopioidreceptor
_version_ 1718421386478747648