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Isolating and characterizing three alternatively spliced mu opioid receptor variants: mMOR-1A, mMOR-1O, and mMOR-1P.


ABSTRACT: Extensive alternative pre-mRNA splicing of the mu opioid receptor gene, OPRM1, has demonstrated an array of splice variants in mice, rats and humans. Three classes of splice variants have been identified: full-length seven transmembrane (TM) domain variants with C-terminal splicing, truncated 6TM variants and single TM variants. The current studies isolates and characterizes an additional three full-length C-terminal splice variants generated from the mouse OPRM1 gene: mMOR-1A, mMOR-1O, and mMOR-1P. Using RT-qPCR, we demonstrated differential expression of these variants' mRNAs among selected brain regions, supporting region-specific alternative splicing. When expressed in Chinese Hamster Ovary cells, all the variants displayed high mu binding affinity and selectivity with subtle differences in the affinities toward some agonists. [³?S]?GTP binding assays revealed marked differences in agonist-induced G protein activation in both potency and efficacy among the variants. Together with the previous studies of mu agonist-induced phosphorylation and internalization in several carboxyl terminal splice variants, the current studies further suggest the existence of biased signaling of various agonists within each individual variant and/or among different variants.

SUBMITTER: Xu J 

PROVIDER: S-EPMC3926657 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Isolating and characterizing three alternatively spliced mu opioid receptor variants: mMOR-1A, mMOR-1O, and mMOR-1P.

Xu Jin J   Xu Mingming M   Bolan Elizabeth E   Gilbert Annie-Kim AK   Pasternak Gavril W GW   Pan Ying-Xian YX  

Synapse (New York, N.Y.) 20140116 4


Extensive alternative pre-mRNA splicing of the mu opioid receptor gene, OPRM1, has demonstrated an array of splice variants in mice, rats and humans. Three classes of splice variants have been identified: full-length seven transmembrane (TM) domain variants with C-terminal splicing, truncated 6TM variants and single TM variants. The current studies isolates and characterizes an additional three full-length C-terminal splice variants generated from the mouse OPRM1 gene: mMOR-1A, mMOR-1O, and mMOR  ...[more]

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