The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
Substitution of a mutant α 2a -adrenergic receptor via “hit and run” gene targeting reveals the role of this subtype in sedative, analgesic, and anesthetic-sparing responses in vivo
Open accessAbstract
Norepinephrine contributes to antinociceptive, sedative, and sympatholytic responses in vivo , and α 2 adrenergic receptor (α 2 AR) agonists are used clinically to mimic these effects. Lack of subtype-specific agonists has prevented elucidation of the role that each α 2 AR subtype (α 2A , α 2B , and α 2C ) plays in these central effects. Here we demonstrate that α 2 AR agonist-elicited sedative, anesthetic-sparing, and analgesic responses are lost in a mouse line expressing a subtly mutated α 2A AR, D79N α 2A AR, created by two-step homologous recombination. These functional changes are accompanied by failure of the D79N α 2A AR to inhibit voltage-gated Ca 2+ currents and spontaneous neuronal firing, a measure of K + current activation. These results provide definitive evidence that the α 2A AR subtype is the primary mediator of clinically important central actions of α 2 AR agonists and suggest that the D79N α 2A AR mouse may serve as a model for exploring other possible α 2A AR functions in vivo .
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Metadata
- Authors
- Lakhlani, P. P., MacMillan, L. B., Guo, T. Z., McCool, B. A., Lovinger, D. M., Maze, M., & Limbird, L. E.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1997-09-02
- Volume
- 94
- Issue
- 18
- Pages
- 9950-9955
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1988468898
- Cited by
- 360
- References
- 39
- FWCI
- 6.64
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Substitution of a mutant α 2a -adrenergic receptor via “hit and run” gene targeting reveals the role of this subtype in sedative, analgesic, and anesthetic-sparing responses in vivo. https://app.cochat.ai/papers/10.1073/pnas.94.18.9950
- The paper
- Lakhlani, P. P., MacMillan, L. B., Guo, T. Z., McCool, B. A., Lovinger, D. M., Maze, M., & Limbird, L. E. (1997). Substitution of a mutant α 2a -adrenergic receptor via “hit and run” gene targeting reveals the role of this subtype in sedative, analgesic, and anesthetic-sparing responses in vivo. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.94.18.9950
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