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Kappa Opioid Receptor Gene and the Regulatory Mechanisms of Its Protein Expression

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The Opiate Receptors

Part of the book series: The Receptors ((REC))

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Abstract

Molecular studies of kappa opioid receptor (KOR) and its gene (Oprk1) were conducted following the cloning of its cDNA and genomic DNA. The KOR gene is mapped to human chromosome 8 and to mouse chromosome 1. Its genomic ­structure and coding sequences are highly conserved among the various ­animal ­species ­examined, and most molecular studies have focused on the mouse clone. The mouse KOR gene spans a distance of approximately 16 kb in length, ­contains three introns, and can produce at least six mature mRNA species due to the use of alternative ­promoters, splicing, and polyadenylation sites. Transcription of the mouse KOR gene is controlled by two promoters that are subjected to ­regulation by various signals such as retinoic acid and nitric oxide, transcription factors, ­chromatin remodeling complexes, and epigenetic events. In addition, the ­expression of endogenous KOR in primary neurons is tightly ­regulated by ­RNA-based ­post-transcriptional mechanisms such as RNA stability and transport, and ­translational regulation. The regulation of KOR protein function has been examined, primarily, in heterologously expressed cell systems, and can involve receptor desensitization, internalization and down-regulation. However, the ­pharmacological and physiological relevance of these findings remain to be validated.

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Acknowledgment

We acknowledge grant supports DA11190, DK54733, DK60521, and K02 DA13926 from NIH, and a Philip Morris award 20093127-A01 to LNW, and DA00564, DA01583, DA11806, and K05-DA70554 from NIH to HHL.

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  1. Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN, 55455, USA

    Li-Na Wei

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  1. Li-Na Wei
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  2. Horace H. Loh
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Correspondence to Li-Na Wei .

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  1. , Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, 10065, New York, USA

    Gavril W. Pasternak

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Wei, LN., Loh, H.H. (2011). Kappa Opioid Receptor Gene and the Regulatory Mechanisms of Its Protein Expression. In: Pasternak, G. (eds) The Opiate Receptors. The Receptors. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-993-2_8

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