Identification and characterization of six new alternatively spliced variants of the human μ opioid receptor gene, OPRM Journal Article
| Authors: | Pan, L.; Xu, J.; Yu, R.; Xu, M. M.; Pan, Y. X.; Pasternak, G. W. |
| Article Title: | Identification and characterization of six new alternatively spliced variants of the human μ opioid receptor gene, OPRM |
| Abstract: | The μ opioid receptor plays an important role in mediating the actions of morphine and morphine-like drugs. Receptor binding and a wide range of pharmacological studies have proposed several μ receptor subtypes, but only one μ opioid receptor (Oprm) gene has been isolated. Like the mouse and rat, the human Oprm gene undergoes alternative splicing. In the present studies, we have identified and characterized six new splice variants from the human Oprm gene using a reverse transcription-polymerase chain reaction strategy, yielding a total of 10 human splice variants of the μ opioid receptor MOR-1. All the variants identified contained exons 1, 2 and 3, but differed from MOR-1 itself and each other by splicing downstream from exon 3, resulting in different amino acid sequences. Northern blot analysis demonstrated expression of the variant mRNAs. Receptor binding assays established that these variants belonged to the μ opioid receptor family with limited differences in μ opioid ligand affinities and selectivity. However, adenylyl cyclase and [35S] GTPγS binding assays revealed major differences in both potency and efficacy among these variants. The dissociation between binding affinity, potency and efficacy for the opioids among these variants may provide insights into the wide range of opioid responses among these agents observed clinically and opens new avenues in designing selective drugs based upon their efficacy and potency rather simple binding affinity. © 2005 IBRO. Published by Elsevier Ltd. All rights reserved. |
| Keywords: | controlled study; unclassified drug; human cell; exon; exons; nonhuman; binding affinity; animals; reverse transcription polymerase chain reaction; gene expression; opiate; drug design; amino acid sequence; molecular sequence data; messenger rna; reverse transcriptase polymerase chain reaction; rna, messenger; gene identification; nucleotide sequence; ligand; alternative splicing; ligands; base sequence; amino acid; dna primers; morphine; analgesics, opioid; blotting, northern; protein variant; mu opiate receptor; receptors, opioid, mu; isoprotein; dissociation; receptor binding; rna splicing; northern blotting; adenylate cyclase; cho cells; cricetinae; guanosine 5'-o-(3-thiotriphosphate); mor-1; gene isolation; variation (genetics); forskolin; μ receptor; mu opiate receptor 1 [1-3]; mu opiate receptor 1 a; mu opiate receptor 1 b 1; mu opiate receptor 1 b 2; mu opiate receptor 1 b 3; mu opiate receptor 1 b 4; mu opiate receptor 1 b 5; mu opiate receptor 1 wt; mu opiate receptor 1 y |
| Journal Title: | Neuroscience |
| Volume: | 133 |
| Issue: | 1 |
| ISSN: | 0306-4522 |
| Publisher: | Pergamon-Elsevier Science Ltd |
| Date Published: | 2005-01-01 |
| Start Page: | 209 |
| End Page: | 220 |
| Language: | English |
| DOI: | 10.1016/j.neuroscience.2004.12.033 |
| PUBMED: | 15893644 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 53" - "Export Date: 24 October 2012" - "CODEN: NRSCD" - "Molecular Sequence Numbers: GENBANK: AY225404, AY309001, AY309005, AY309006, AY309007, AY309008, AY309009;" - "Source: Scopus" |
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