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Published on: July 3, 2015
Mu opiate receptor subtypes
1Neuroscience Research Institute, State University of New York, College at Old Westbury, Old Westbury, NY, U.S.A.
Abstract:
The . opiate receptor gene (MOR) has at least 14 exons that can generate 15 different splice variants. Recently, two new human MOR splice variants (hMOR-1O and hMOR-1X) have been identified and characterized. The two variants containing human MOR exons 1, 2, and 3 and a fourth alternative exon O, or exon X, are expressed in human brain tissue, and are selective for mu opioid binding in transfected cells. It is unclear; however, what the biologic role of these two novel human splice variants is in vivo. The mu3 opiate receptor subtype found in various human tissues where it is coupled to constitutive nitric oxide synthase derived nitric oxide release is characterized by its opiate alkaloid selectivity and its insensitivity to opioid peptides. The mu3 clone exhibits 100% identity to the mu1 receptor subtype in the center and conserved region, but with a truncated 5'-end (position 503 of mu1 mRNA) (missing several hundred nucleotides). In addition, the 3'-end of the new clone contains the 3'-end of the mu1 receptor, followed by a new fragment of 263 bases, and then by a 202 bp fragment of the 3'-end of the mu1 gene untranslated region. When mu3 is expressed in a heterologous system, the protein produced from this cDNA exhibits all of the expected biochemical characteristics of the mu3 receptor. The isolation of this novel splice variant adds support to the presence of morphinergic signaling in animals.
Insights
Two novel human mu-opiate receptor (MOR) splice variants, hMOR-1O and hMOR-1X, were identified in brain tissue. Their specific in vivo biological roles require further investigation.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- The human opiate receptor gene (MOR) generates at least 15 splice variants from 14 exons.
- Recent identification of two new variants, hMOR-1O and hMOR-1X, expands understanding of MOR gene expression.
Purpose of the Study:
- To characterize the novel human MOR splice variants hMOR-1O and hMOR-1X.
- To investigate the biochemical characteristics and potential function of the mu3 opiate receptor subtype.
Main Methods:
- Expression analysis of hMOR-1O and hMOR-1X in human brain tissue.
- Transfection studies to assess mu opioid binding selectivity.
- Molecular cloning and heterologous expression of the mu3 opiate receptor subtype.
Main Results:
- hMOR-1O and hMOR-1X contain human MOR exons 1, 2, and 3 with alternative exon O or X.
- These variants are expressed in human brain and show selective mu opioid binding.
- The mu3 clone, a novel splice variant, exhibits 100% identity to mu1 in conserved regions but has a truncated 5'-end and altered 3'-end.
- Expressed mu3 protein displays expected biochemical characteristics of the mu3 receptor.
Conclusions:
- The novel splice variants hMOR-1O and hMOR-1X are expressed in human brain tissue.
- The characterization of the mu3 receptor subtype provides evidence for morphinergic signaling in animals.
- Further research is needed to elucidate the in vivo biological roles of hMOR-1O and hMOR-1X.
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