The opioid ligand binding of human mu-opioid receptor is modulated by novel splice variants of the receptor.

The pharmacological actions of morphine and morphine-like drugs, such as heroin, mediate primarily through the mu-opioid receptor (MOR). It has been proposed that the functional diversity of MOR may be related to alternative splicing of the MOR gene. Although a number of MOR mRNA splice variants have been reported, their biological function has been controversial. In this study, two novel splice variants of the human MOR gene were discovered. Splice variants 1 and 2 (here called the SV1 and SV2) retain different portions of intron I. In vitro translation of SV1 and SV2 produced proteins with the predicted molecular weights. The splice variant proteins were identical to the wild-type MOR-1 up to the first transmembrane domains, but were different after the first intracellular loop domains. SV1 and SV2 of hMOR were present in human neuroblastoma NMB cells and human whole brain confirmed by RT-PCR. In a receptor binding assay, cells expressing the SV1 and SV2 do not exhibit binding to [(3)H]diprenorphine. The formations of MOR.SV1 and MOR.SV2 heterodimers were demonstrated by co-immunoprecipitation and bioluminescence resonance energy transfer between MOR and splice variants. Co-transfection of MOR-GFP and SV-DsRed gene showed that MOR and SV protein co-localized at the cytoplasmic membrane. In NMB cells expressing human MOR gene, transfection of SV1 or SV2 reduced binding activity of the endogenous MOR. These data support a potential role of SV1 and SV2 proteins as possible biological modulator of human mu-opioid receptor.

Citation

Hack Sun Choi, Chun Sung Kim, Cheol Kyu Hwang, Kyu Young Song, Wei Wang, Yu Qiu, Ping-Yee Law, Li-Na Wei, Horace H Loh. The opioid ligand binding of human mu-opioid receptor is modulated by novel splice variants of the receptor. Biochemical and biophysical research communications. 2006 May 19;343(4):1132-40

Mesh Tags

Substances

PMID: 16580639

search → result