A118G Mu Opioid Receptor polymorphism increases inhibitory effects on Ca V2.2 channels

Autores
López Soto, Eduardo Javier; Raingo, Jesica
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Single nucleotide polymorphisms (SNPs) in the human OPRM1 gene result in common variants of Mu Opioid Receptors (hMORs). The A118G SNP occurs at high frequency in certain human populations and produces an aminoacidic substitution: N40D (hMOR-N to hMOR-D) at protein level. N40D is reported to alter pain thresholds and morphine efficacy. hMORs inhibit Ca V2.2 channels (N-type currents) at presynaptic nociceptor terminals in dorsal horn, thus reducing calcium influx, transmitter release, and transmission of noxious signals. Nociceptors express different splice isoforms of Ca V2.2. Isoforms distinguished by the presence of alternatively spliced exon e37a are of interest because channels containing e37a are particularly enriched in nociceptors. Recent studies showed that Ca V2.2e37a is more sensitive to inhibition by Mu Opioid Receptors than the ubiquitous splice variant Ca V2.2e37b. Here, we evaluate the effect of hMOR-N and hMOR-D on cloned Ca V2.2e37a channels expressed in mammalian cells. We observe that hMOR-D inhibits Ca V2.2e37a currents at agonist concentrations 4-fold lower than those needed to inhibit Ca V2.2e37a currents by the same degree via hMOR-N. We observe little difference in hMOR-D and hMOR-N inhibition of Ca V2.2e37b currents. Our study demonstrates that this common site of OPRM1 polymorphism affects the inhibitory actions of MORs on both major Ca V2.2 isoforms expressed in nociceptors. © 2012 Elsevier Ireland Ltd.
Fil: López Soto, Eduardo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Fil: Raingo, Jesica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Materia
A118g
Ca V2.2
Calcium Channel
G Protein
Mu Opioids Receptor
Pain
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/67609
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/67609
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A118G Mu Opioid Receptor polymorphism increases inhibitory effects on Ca V2.2 channelsLópez Soto, Eduardo JavierRaingo, JesicaA118gCa V2.2Calcium ChannelG ProteinMu Opioids ReceptorPainhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Single nucleotide polymorphisms (SNPs) in the human OPRM1 gene result in common variants of Mu Opioid Receptors (hMORs). The A118G SNP occurs at high frequency in certain human populations and produces an aminoacidic substitution: N40D (hMOR-N to hMOR-D) at protein level. N40D is reported to alter pain thresholds and morphine efficacy. hMORs inhibit Ca V2.2 channels (N-type currents) at presynaptic nociceptor terminals in dorsal horn, thus reducing calcium influx, transmitter release, and transmission of noxious signals. Nociceptors express different splice isoforms of Ca V2.2. Isoforms distinguished by the presence of alternatively spliced exon e37a are of interest because channels containing e37a are particularly enriched in nociceptors. Recent studies showed that Ca V2.2e37a is more sensitive to inhibition by Mu Opioid Receptors than the ubiquitous splice variant Ca V2.2e37b. Here, we evaluate the effect of hMOR-N and hMOR-D on cloned Ca V2.2e37a channels expressed in mammalian cells. We observe that hMOR-D inhibits Ca V2.2e37a currents at agonist concentrations 4-fold lower than those needed to inhibit Ca V2.2e37a currents by the same degree via hMOR-N. We observe little difference in hMOR-D and hMOR-N inhibition of Ca V2.2e37b currents. Our study demonstrates that this common site of OPRM1 polymorphism affects the inhibitory actions of MORs on both major Ca V2.2 isoforms expressed in nociceptors. © 2012 Elsevier Ireland Ltd.Fil: López Soto, Eduardo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Raingo, Jesica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaElsevier Ireland2012-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/67609López Soto, Eduardo Javier; Raingo, Jesica; A118G Mu Opioid Receptor polymorphism increases inhibitory effects on Ca V2.2 channels; Elsevier Ireland; Neuroscience Letters; 523; 2; 6-2012; 190-1940304-3940CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.neulet.2012.06.074info:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0304394012009068info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:34:04Zoai:ri.conicet.gov.ar:11336/67609instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:34:04.615CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A118G Mu Opioid Receptor polymorphism increases inhibitory effects on Ca V2.2 channels
title A118G Mu Opioid Receptor polymorphism increases inhibitory effects on Ca V2.2 channels
spellingShingle A118G Mu Opioid Receptor polymorphism increases inhibitory effects on Ca V2.2 channels
López Soto, Eduardo Javier
A118g
Ca V2.2
Calcium Channel
G Protein
Mu Opioids Receptor
Pain
title_short A118G Mu Opioid Receptor polymorphism increases inhibitory effects on Ca V2.2 channels
title_full A118G Mu Opioid Receptor polymorphism increases inhibitory effects on Ca V2.2 channels
title_fullStr A118G Mu Opioid Receptor polymorphism increases inhibitory effects on Ca V2.2 channels
title_full_unstemmed A118G Mu Opioid Receptor polymorphism increases inhibitory effects on Ca V2.2 channels
title_sort A118G Mu Opioid Receptor polymorphism increases inhibitory effects on Ca V2.2 channels
dc.creator.none.fl_str_mv López Soto, Eduardo Javier
Raingo, Jesica
author López Soto, Eduardo Javier
author_facet López Soto, Eduardo Javier
Raingo, Jesica
author_role author
author2 Raingo, Jesica
author2_role author
dc.subject.none.fl_str_mv A118g
Ca V2.2
Calcium Channel
G Protein
Mu Opioids Receptor
Pain
topic A118g
Ca V2.2
Calcium Channel
G Protein
Mu Opioids Receptor
Pain
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Single nucleotide polymorphisms (SNPs) in the human OPRM1 gene result in common variants of Mu Opioid Receptors (hMORs). The A118G SNP occurs at high frequency in certain human populations and produces an aminoacidic substitution: N40D (hMOR-N to hMOR-D) at protein level. N40D is reported to alter pain thresholds and morphine efficacy. hMORs inhibit Ca V2.2 channels (N-type currents) at presynaptic nociceptor terminals in dorsal horn, thus reducing calcium influx, transmitter release, and transmission of noxious signals. Nociceptors express different splice isoforms of Ca V2.2. Isoforms distinguished by the presence of alternatively spliced exon e37a are of interest because channels containing e37a are particularly enriched in nociceptors. Recent studies showed that Ca V2.2e37a is more sensitive to inhibition by Mu Opioid Receptors than the ubiquitous splice variant Ca V2.2e37b. Here, we evaluate the effect of hMOR-N and hMOR-D on cloned Ca V2.2e37a channels expressed in mammalian cells. We observe that hMOR-D inhibits Ca V2.2e37a currents at agonist concentrations 4-fold lower than those needed to inhibit Ca V2.2e37a currents by the same degree via hMOR-N. We observe little difference in hMOR-D and hMOR-N inhibition of Ca V2.2e37b currents. Our study demonstrates that this common site of OPRM1 polymorphism affects the inhibitory actions of MORs on both major Ca V2.2 isoforms expressed in nociceptors. © 2012 Elsevier Ireland Ltd.
Fil: López Soto, Eduardo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Fil: Raingo, Jesica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
description Single nucleotide polymorphisms (SNPs) in the human OPRM1 gene result in common variants of Mu Opioid Receptors (hMORs). The A118G SNP occurs at high frequency in certain human populations and produces an aminoacidic substitution: N40D (hMOR-N to hMOR-D) at protein level. N40D is reported to alter pain thresholds and morphine efficacy. hMORs inhibit Ca V2.2 channels (N-type currents) at presynaptic nociceptor terminals in dorsal horn, thus reducing calcium influx, transmitter release, and transmission of noxious signals. Nociceptors express different splice isoforms of Ca V2.2. Isoforms distinguished by the presence of alternatively spliced exon e37a are of interest because channels containing e37a are particularly enriched in nociceptors. Recent studies showed that Ca V2.2e37a is more sensitive to inhibition by Mu Opioid Receptors than the ubiquitous splice variant Ca V2.2e37b. Here, we evaluate the effect of hMOR-N and hMOR-D on cloned Ca V2.2e37a channels expressed in mammalian cells. We observe that hMOR-D inhibits Ca V2.2e37a currents at agonist concentrations 4-fold lower than those needed to inhibit Ca V2.2e37a currents by the same degree via hMOR-N. We observe little difference in hMOR-D and hMOR-N inhibition of Ca V2.2e37b currents. Our study demonstrates that this common site of OPRM1 polymorphism affects the inhibitory actions of MORs on both major Ca V2.2 isoforms expressed in nociceptors. © 2012 Elsevier Ireland Ltd.
publishDate 2012
dc.date.none.fl_str_mv 2012-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/67609
López Soto, Eduardo Javier; Raingo, Jesica; A118G Mu Opioid Receptor polymorphism increases inhibitory effects on Ca V2.2 channels; Elsevier Ireland; Neuroscience Letters; 523; 2; 6-2012; 190-194
0304-3940
CONICET Digital
CONICET
url http://hdl.handle.net/11336/67609
identifier_str_mv López Soto, Eduardo Javier; Raingo, Jesica; A118G Mu Opioid Receptor polymorphism increases inhibitory effects on Ca V2.2 channels; Elsevier Ireland; Neuroscience Letters; 523; 2; 6-2012; 190-194
0304-3940
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.neulet.2012.06.074
info:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0304394012009068
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Ireland
publisher.none.fl_str_mv Elsevier Ireland
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.069144

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