Cited by 213Neuropeptides and Animal PhysiologyReceptor Mechanisms and SignalingNeurotransmitter Receptor Influence on Behavior

The single nucleotide polymorphism A118G alters functional properties of the human mu opioid receptor

Kroslak, Thomas, LaForge, K. Steven, Gianotti, Robert J., Ho, Ann, Nielsen, David A., Kreek, Mary Jeanne·2007·Journal of Neurochemistry

Abstract

The most common single nucleotide polymorphism in the coding region of the human mu opioid receptor gene is the A118G variant, an adenine to guanine transition at nucleotide position 118 of the coding sequence of the gene. This polymorphism codes for an asparagine to aspartic acid substitution at amino acid 40 in the amino‐terminus, thereby removing a potential extracellular glycosylation site. Using in vitro cellular expression assays, this variant has been reported to change binding of the endogenous agonist beta‐endorphin and signaling of the receptor following binding of beta‐endorphin. Three clinical studies report that A118G genotype affects opioid antagonist‐mediated increases in cortisol levels. These studies demonstrate a functional role of this variant in responses to endogenous and exogenous opioids. To further characterize function, we expressed the prototype and variant receptors in two types of cells (human 293 embryonic kidney cells and Syrian hamster adenovirus‐12‐induced tumor cells). Stable expression of variant and prototype receptors was characterized by differences in levels of cell surface binding capacity (Bmax), forskolin‐induced cAMP accumulation, as well as agonist‐induced accumulation of cAMP (EC 50) for several agonists, but not for beta‐endorphin. In contrast, transiently expressed variant receptors showed only a minor difference in cell surface binding capacity compared to the prototype, and no differences in cAMP EC 50 values.

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Crossref · 10.1111/j.1471-4159.2007.04738.x

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Authors
Kroslak, T., LaForge, K. S., Gianotti, R. J., Ho, A., Nielsen, D. A., & Kreek, M. J.
Affiliations
Rockefeller University (US)
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2007-06-03
Volume
103
Issue
1
Pages
77-87
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
OpenAlex
W2039877085
Cited by
213
References
42
Citations by year
2026: 3 · 2024: 3 · 2023: 7 · 2022: 7 · 2021: 4 · 2020: 9 · 2019: 8 · 2018: 9 · 2017: 11 · 2016: 9 · 2015: 16 · 2014: 21 · 2013: 17 · 2012: 23
FWCI
6.21
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Neurochemistry (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • Biotechnology and Biological Sciences Research Council (C17893)
  • National Institute on Drug Abuse (R01DA012848, P60 DA 05130, P60DA005130, R01-DA-12848)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
mu-opioid receptor, A118G polymorphism, single nucleotide polymorphisms, cAMP signaling, forskolin, cell surface binding
MeSH terms
Cyclic AMP, Analgesics, Opioid, Animals, Binding, Competitive, Cell Line, Cell Membrane, Dose-Response Relationship, Drug, Fibroblasts, Colforsin, Cricetinae, Humans, Kidney, Mesocricetus, Receptors, Opioid, mu, Gene Transfer Techniques, Polymorphism, Single Nucleotide, Enkephalin, Ala(2)-MePhe(4)-Gly(5)-

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