Identification and characterization of six new alternatively spliced variants of the human μ opioid receptor gene, Oprm

L Pan, J Xu, R Yu, MM Xu, YX Pan, GW Pasternak - Neuroscience, 2005 - Elsevier
L Pan, J Xu, R Yu, MM Xu, YX Pan, GW Pasternak
Neuroscience, 2005Elsevier
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 …
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.
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