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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/67609
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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 Técnicas2025-09-03T09:44:19Zoai: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:34982025-09-03 09:44:19.572CONICET 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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13.13397 |