Functional analysis of MOR-1 splice variants of the mouse mu opioid receptor gene Oprm Journal Article
| Authors: | Bolan, E. A.; Pan, Y. X.; Pasternak, G. W. |
| Article Title: | Functional analysis of MOR-1 splice variants of the mouse mu opioid receptor gene Oprm |
| Abstract: | A series of mu opioid receptor gene Oprm splice variants have been reported that differ only at their C-terminus. These variants all contain exons 1, 2, and 3 of the gene, the exons responsible for coding all seven transmembrane domains. Whereas MOR-1 also has exon 4 that encodes for an additional 12 amino acids at the tip of the C-terminus, the other MOR-1 variants have unique amino acid sequences distinct from those in MOR-1 due to alternative splicing. All these variants are mu-selective in binding assays. The current study explored the ability of these variants to stimulate [ 35S]GTPγS binding to assess them functionally. Only mu opioids stimulated [35S]GTPγS binding. Among the mu opioids we noted marked differences in their maximal stimulation among the clones. This was most prominent with β-endorphin, which stimulated [35S]GTPγS binding in the MOR-1E expressing cells to a greater degree than [D-Ala 2,MePhe4,Gly(ol)5]enkephalin (DAMGO; 130%) and was far less effective than DAMGO in MOR-1C cells (44%). The rank order of maximal stimulation of the drugs varied among the clones as well. Dynorphin A, β-endorphin and morphine were most effective in stimulating [ 35S]GTPγS binding in MOR-1E, while M6G and fentanyl were most effective in MOR-1 expressing cells. The potency (EC50) of some of the drugs also varied extensively among the clones, with a poor correlation between the potency of the drugs to stimulate [35S]GTPγS binding and their binding affinity. Together, these findings reveal marked functional differences among the variants that only can be explained by their structural differences at the tip of their C-terminus. © 2003 Wiley-Liss, Inc. |
| Keywords: | nonhuman; animal cell; mouse; animals; mice; gene; carboxy terminal sequence; protein binding; structure activity relation; amino acid sequence; molecular sequence data; alternative splicing; receptor affinity; methadone; morphine; mu opiate receptor; receptors, opioid, mu; receptor binding; fentanyl; enkephalin[2,5 dextro penicillamine]; morphine 6 glucuronide; splicing; cho cell; cho cells; cricetinae; oprm gene; neurochemistry; 3,4 dichloro n methyl n [2 (1 pyrrolidinyl)cyclohexyl]benzeneacetamide methanesulfonate; dynorphin a; mor-1; g-protein; gene isolation; variation (genetics); enkephalin[2 dextro alanine 4 methylphenylalanine 5 glycine]; guanosine 5' o (3 thiotriphosphate); mop-1; priority journal; article; gtpγs; mu opioid receptor subtypes; beta endorphin; endomorphin 1; endomorphin 2 |
| Journal Title: | Synapse |
| Volume: | 51 |
| Issue: | 1 |
| ISSN: | 0887-4476 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2004-01-01 |
| Start Page: | 11 |
| End Page: | 18 |
| Language: | English |
| DOI: | 10.1002/syn.10277 |
| PROVIDER: | scopus |
| PUBMED: | 14579421 |
| DOI/URL: | |
| Notes: | Synapse -- Cited By (since 1996):43 -- Export Date: 16 June 2014 -- CODEN: SYNAE -- Source: Scopus |
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