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  • 1. Olsen, Richard W.
    et al.
    Li, Guo-Dong
    Wallner, Martin
    Trudell, James R.
    Bertaccini, Edward J.
    Lindahl, Erik
    KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical & Computational Biophysics.
    Miller, Keith W.
    Alkana, Ronald L.
    Davies, Daryl L.
    Structural Models of Ligand-Gated Ion Channels: Sites of Action for Anesthetics and Ethanol2014In: Alcoholism: Clinical and Experimental Research, ISSN 0145-6008, E-ISSN 1530-0277, Vol. 38, no 3, p. 595-603Article in journal (Refereed)
    Abstract [en]

    The molecular mechanism(s) of action of anesthetic, and especially, intoxicating doses of alcohol (ethanol [EtOH]) have been of interest even before the advent of the Research Society on Alcoholism. Recent physiological, genetic, and biochemical studies have pin-pointed molecular targets for anesthetics and EtOH in the brain as ligand-gated ion channel (LGIC) membrane proteins, especially the pentameric (5 subunit) Cys-loop superfamily of neurotransmitter receptors including nicotinic acetylcholine (nAChRs), GABA(A) (GABA(A)Rs), and glycine receptors (GlyRs). The ability to demonstrate molecular and structural elements of these proteins critical for the behavioral effects of these drugs on animals and humans provides convincing evidence for their role in the drugs' actions. Amino acid residues necessary for pharmacologically relevant allosteric modulation of LGIC function by anesthetics and EtOH have been identified in these channel proteins. Site-directed mutagenesis revealed potential allosteric modulatory sites in both the trans-membrane domain (TMD) and extracellular domain (ECD). Potential sites of action and binding have been deduced from homology modeling of other LGICs with structures known from crystallography and cryo-electron microscopy studies. Direct information about ligand binding in the TMD has been obtained by photoaffinity labeling, especially in GABA(A)Rs. Recent structural information from crystallized procaryotic (ELIC and GLIC) and eukaryotic (GluCl) LGICs allows refinement of the structural models including evaluation of possible sites of EtOH action.

  • 2. Voigt, T. B.
    et al.
    Heusser, S.
    KTH.
    Klement, Göran
    KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical & Computational Biophysics.
    Pouya, Iman
    KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical & Computational Biophysics.
    Mola, A. R.
    Ruel, T. M. D.
    Trudell, J. R.
    Lindahl, Erik
    KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical & Computational Biophysics.
    Howard, R. J.
    Physicochemical determinants of alcohol binding in a model ligand-gated ion channel2015In: Alcohol and Alcoholism, ISSN 0735-0414, E-ISSN 1464-3502, Vol. 50Article in journal (Other academic)
  • 3.
    Örtendahl, Monica
    et al.
    KTH, School of Architecture and the Built Environment (ABE), Transport and Economics (closed 20110301), Safety Research (closed 20110301).
    Näsman, Per
    KTH, School of Architecture and the Built Environment (ABE), Transport and Economics (closed 20110301), Safety Research (closed 20110301).
    Factors Affecting Continuation of Smoking by Pregnant and Non-pregnant Women2009In: Substance Abuse, ISSN 0889-7077, E-ISSN 1573-6733, Vol. 30, no 2, p. 150-157Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to test a framework based upon the value and the probability of outcomes related to smoking. Over a 2-week period, 80 women were asked to perform judgments of value and probability of the outcome for smoking-related consequences. Subgroups were formed by the two variables of pregnancy and intent to quit smoking. Judgments were performed given the conditions of quitting and not quitting smoking. The intent to quit or not quit smoking had an impact on expected utility of smoking. Moreover, there was a difference between expected utility given the conditions of not quitting smoking and quitting smoking. A framework based upon values and beliefs appears to be useful in describing the addictive behavior of smoking and can be applied in developing smoking-cessation education.

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