Artículo
A118G Mu Opioid Receptor polymorphism increases inhibitory effects on Ca V2.2 channels
Fecha de publicación:
06/2012
Editorial:
Elsevier Ireland
Revista:
Neuroscience Letters
ISSN:
0304-3940
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
A118g
,
Ca V2.2
,
Calcium Channel
,
G Protein
,
Mu Opioids Receptor
,
Pain
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Colecciones
Articulos(IMBICE)
Articulos de INST.MULTIDISCIPL.DE BIOLOGIA CELULAR (I)
Articulos de INST.MULTIDISCIPL.DE BIOLOGIA CELULAR (I)
Citación
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
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