IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v389y1997i6649d10.1038_38738.html
   My bibliography  Save this article

Sites of alcohol and volatile anaesthetic action on GABAA and glycine receptors

Author

Listed:
  • S. John Mihic

    (University of Colorado Health Sciences Center
    Alcohol Research Center, University of Colorado Health Sciences Center
    Bowman Gray School of Medicine of Wake Forest University)

  • Qing Ye

    (The University of Chicago)

  • Marilee J. Wick

    (University of Colorado Health Sciences Center
    Denver Veteran Administration Medical Center, Alcoholism Research Center)

  • Vladimir V. Koltchine

    (The University of Chicago)

  • Matthew D. Krasowski

    (The University of Chicago)

  • Suzanne E. Finn

    (The University of Chicago)

  • Maria Paola Mascia

    (University of Colorado Health Sciences Center)

  • C. Fernando Valenzuela

    (University of Colorado Health Sciences Center)

  • Kirsten K. Hanson

    (The University of Chicago)

  • Eric P. Greenblatt

    (University of Pennsylvania)

  • R. Adron Harris

    (University of Colorado Health Sciences Center
    Denver Veteran Administration Medical Center, Alcoholism Research Center
    The University of Chicago)

  • Neil L. Harrison

    (The University of Chicago
    The University of Chicago
    The University of Chicago)

Abstract

Volatile anaesthetics have historically been considered to act in a nonspecific manner on the central nervous system1,2. More recent studies, however, have revealed that the receptors for inhibitory neurotransmitters such as γ-aminobutyric acid (GABA) and glycine are sensitive to clinically relevant concentrations of inhaled anaesthetics3. The function of GABAA and glycine receptors is enhanced by a number of anaesthetics4,5,6,7,8,9 and alcohols10,11,12, whereas activity of the related13 GABA ρ1 receptor is reduced14. We have used this difference in pharmacology to investigate the molecular basis for modulation of these receptors by anaesthetics and alcohols. By using chimaeric receptor constructs, we have identified a region of 45 amino-acid residues that is both necessary and sufficient for the enhancement of receptor function. Within this region, two specific amino-acid residues in transmembrane domains 2 and 3 are critical for allosteric modulation of both GABAA and glycine receptors by alcohols and two volatile anaesthetics. These observations support the idea that anaesthetics exert a specific effect on these ion-channel proteins, and allow for the future testing of specific hypotheses of the action of anaesthetics.

Suggested Citation

  • S. John Mihic & Qing Ye & Marilee J. Wick & Vladimir V. Koltchine & Matthew D. Krasowski & Suzanne E. Finn & Maria Paola Mascia & C. Fernando Valenzuela & Kirsten K. Hanson & Eric P. Greenblatt & R. A, 1997. "Sites of alcohol and volatile anaesthetic action on GABAA and glycine receptors," Nature, Nature, vol. 389(6649), pages 385-389, September.
  • Handle: RePEc:nat:nature:v:389:y:1997:i:6649:d:10.1038_38738
    DOI: 10.1038/38738
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/38738
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/38738?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Vernon A. Benignus & Philip J. Bushnell & William K. Boyes, 2005. "Toward Cost‐Benefit Analysis of Acute Behavioral Effects of Toluene in Humans," Risk Analysis, John Wiley & Sons, vol. 25(2), pages 447-456, April.
    2. Arvind Kumar & Kayla Kindig & Shanlin Rao & Afroditi-Maria Zaki & Sandip Basak & Mark S. P. Sansom & Philip C. Biggin & Sudha Chakrapani, 2022. "Structural basis for cannabinoid-induced potentiation of alpha1-glycine receptors in lipid nanodiscs," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Toshikazu Sasabe & Shoichi Ishiura, 2010. "Alcoholism and Alternative Splicing of Candidate Genes," IJERPH, MDPI, vol. 7(4), pages 1-19, March.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:389:y:1997:i:6649:d:10.1038_38738. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.