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• W2080822597 abstract "Abstract Mu opioid receptors mediate the pharmacological actions of morphine and morphine‐like drugs, such as heroin. The mouse and human Oprm genes undergo splicing. In these present studies, we have identified and characterized three new MOR‐1 splice variants from the rat Oprm gene. Using an RT‐PCR approach, we isolated the new exons 7, 8 and 9 downstream of exon 3. The rat exons 7 and 9 were homologous to the mouse exons 7 and 9 while the rat exon 8 was not. Northern blot analysis with the new exon probes showed distinctive and abundant transcripts of the variants in the rat brain. Full‐length cDNA clones containing the new exons, rMOR‐1C1, rMOR‐1C2 and rMOR‐1D were obtained using an RT‐PCR approach. Each contained the same exons 1, 2 and 3 as the original rMOR‐1, followed by different combinations of the new exons in place of exon 4. In addition, we also isolated another new variant, rMOR‐1A, which contains only exons 1, 2 and 3, and is homologous to the human variant MOR‐1A previously identified. All the variants were highly mu‐selective in binding studies with little difference in affinities for the mu ligands among the variants. However, functional evaluation of assessments of the variants using agonist stimulated [ 35 S]GTPγS binding assays revealed marked differences among the variants, both in terms of potency and efficacy of the drugs. The relative efficacy of a series of mu opioids to each other varied depending upon the variant studied. Efficacy in the [ 35 S]GTPγS assay did not correlate with either receptor binding affinity or with potency. Thus, selectivity of opioid action might be achieved by designing compounds with varying efficacies at different MOR‐1 variants." @default.
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• W2080822597 date "2004-10-27" @default.
• W2080822597 modified "2023-10-16" @default.
• W2080822597 title "Identification of three new alternatively spliced variants of the rat mu opioid receptor gene: dissociation of affinity and efficacy" @default.
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• W2080822597 doi "https://doi.org/10.1111/j.1471-4159.2004.02767.x" @default.
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