Isolation and characterization of new exon 11-associated N-terminal splice variants of the human mu opioid receptor gene Journal Article
| Authors: | Xu, J.; Xu, M.; Hurd, Y. L.; Pasternak, G. W.; Pan, Y. X. |
| Article Title: | Isolation and characterization of new exon 11-associated N-terminal splice variants of the human mu opioid receptor gene |
| Abstract: | Alternative splicing of the mu opioid receptor genes to create multiple mu receptor subtypes has been demonstrated in animals and humans. Previously, we identified a number of C-terminal variants in mice, rats and human, followed by several N-terminal variants associated with a new upstream exon in mice (exon 11). Behavioral studies in exon 11 knockout mice suggest an important role for the exon 11 variants in the analgesic actions of heroin and morphine-6β- glucuronide, but not morphine or methadone. We now have identified a homologous human exon 11 and three similar human exon 11-associated variants, suggesting conservation of exon 11 and its associated variants across species. hMOR-1i has an additional 93 amino acids at the tip of the N-terminus but is otherwise identical to hMOR-1. When expressed in Chinese hamster ovary cells, the additional 93 amino acids in hMOR-1i had little effect on opioid binding, but significantly altered agonist-induced G-protein activation. hMOR-1G1 and hMOR-1G2 predicted six transmembrane domain variants, similar to those seen in mice. The regional expression of these exon 11-associated variants, as determined by RT-PCR, varied markedly, implying region-specific alternative splicing. The presence of exon 11-associated variants in humans raises questions regarding their potential role in heroin and morphine-6β-glucuronide actions in people as they do in mice. © 2009 The Authors. |
| Keywords: | controlled study; protein expression; exon; exons; nonhuman; protein domain; animal cell; mouse; animals; mice; mus; gene expression; opiate; genetic variability; animalia; evolution, molecular; gene activation; dna; conserved sequence; molecular sequence data; sequence homology, amino acid; species specificity; amino terminal sequence; messenger rna; alternative splicing; protein structure, tertiary; rattus; morphine; sequence homology, nucleic acid; guanine nucleotide binding protein; mu opiate receptor; receptors, opioid, mu; protein isoforms; rna splicing; g protein; mu opioid receptor (mor); mu opioid receptor-1; opioid receptor; splicing; cho cell; cho cells; cricetinae; cricetulus; cricetulus griseus |
| Journal Title: | Journal of Neurochemistry |
| Volume: | 108 |
| Issue: | 4 |
| ISSN: | 0022-3042 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2009-02-01 |
| Start Page: | 962 |
| End Page: | 972 |
| Language: | English |
| DOI: | 10.1111/j.1471-4159.2008.05833.x |
| PUBMED: | 19077058 |
| PROVIDER: | scopus |
| PMCID: | PMC2727151 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 5" - "Export Date: 30 November 2010" - "CODEN: JONRA" - "Source: Scopus" |
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