MolPharm

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zuo, Y.
Right arrow Articles by Narahashi, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zuo, Y.
Right arrow Articles by Narahashi, T.

Vol. 60, Issue 4, 700-711, October 2001

Dual Action of n-Alcohols on Neuronal Nicotinic Acetylcholine Receptors

Yi Zuo, Gary L. Aistrup, William Marszalec, Alison Gillespie, Laura E. Chavez-Noriega, Jay Z. Yeh, and Toshio Narahashi

Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, Illinois (Y.Z., G.L.A., W.M., J.Z.Y., T.N.); and Merck Research Laboratories-San Diego, La Jolla, California (A.G., L.E.C.-N.)

Alcohol is known to modulate the activity of a variety of neuroreceptors and ion channels. Recently, neuronal nicotinic acetylcholine receptors (nnAChRs) have become a specific focus of study because not only are they potently modulated by alcohol but also they regulate the release of various transmitters, including gamma -aminobutyric acid (GABA) and dopamine, which play an important role in the behavioral effects of ethanol. Whereas the potency of normal alcohols (n-alcohols) to potentiate GABAA receptors and to inhibit N-methyl-D-aspartate receptors increases with carbon chain length, we have found that n-alcohols, depending on the carbon chain length, exert a dual action, potentiation and inhibition, on nnAChRs in primary cultured rat cortical neurons. The mechanism of dual action of n-alcohols on nnAChRs was further analyzed using human embryonic kidney cells expressing the alpha 4beta 2 subunits. Shorter chain alcohols from methanol to n-propanol potentiated acetylcholine (ACh)-induced currents, whereas longer chain alcohols from n-pentanol to n-dodecanol inhibited the currents. n-Butanol either potentiated or inhibited the currents depending on the concentrations of ACh and butanol. The parameters for both potentiation (log EC200) and inhibition (log IC50) were linearly related to carbon number, albeit with different slopes. The slope for potentiation was -0.299, indicating a change in free energy change (Delta Delta G) of 405 cal/mol/methylene group, whereas the slope for inhibition was -0.584, indicating a Delta Delta G of 792 cal/mol. These results suggest that potentiating and inhibitory actions are exerted through two different binding sites. Ethanol decreased the potency of n-octanol to inhibit ACh currents, possibly resulting from an allosteric mechanism.

Copyright © 2001 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Pharmacol. Rev.Home page
A. M. Dopico and D. M. Lovinger
Acute Alcohol Action and Desensitization of Ligand-Gated Ion Channels
Pharmacol. Rev., March 1, 2009; 61(1): 98 - 114.
[Abstract] [Full Text] [PDF]

Home page
 Anesth. Analg.Home page
L. Yang and J. M. Sonner
Anesthetic-Like Modulation of Receptor Function by Surfactants: A Test of the Interfacial Theory of Anesthesia
Anesth. Analg., September 1, 2008; 107(3): 868 - 874.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
T. Horishita and R. A. Harris
n-Alcohols Inhibit Voltage-Gated Na+ Channels Expressed in Xenopus Oocytes
J. Pharmacol. Exp. Ther., July 1, 2008; 326(1): 270 - 277.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
L. M. Broad, R. Zwart, K. H. Pearson, M. Lee, L. Wallace, G. I. McPhie, R. Emkey, S. P. Hollinshead, C. P. Dell, S. R. Baker, et al.
Identification and Pharmacological Profile of a New Class of Selective Nicotinic Acetylcholine Receptor Potentiators
J. Pharmacol. Exp. Ther., September 1, 2006; 318(3): 1108 - 1117.
[Abstract] [Full Text] [PDF]

Home page
 Anesth. Analg.Home page
R. J. N. Stevens, D. Rusch, P. A. Davies, and D. E. Raines
Molecular Properties Important for Inhaled Anesthetic Action on Human 5-HT3A Receptors
Anesth. Analg., June 1, 2005; 100(6): 1696 - 1703.
[Abstract] [Full Text] [PDF]

Home page
 Arch Gen PsychiatryHome page
E. C. Nelson, A. C. Heath, K. K. Bucholz, P. A. F. Madden, Q. Fu, V. Knopik, M. T. Lynskey, M. T. Lynskey, J. B. Whitfield, D. J. Statham, et al.
Genetic Epidemiology of Alcohol-Induced Blackouts
Arch Gen Psychiatry, March 1, 2004; 61(3): 257 - 263.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
C. M. Borghese, L. A. Henderson, V. Bleck, J. R. Trudell, and R. A. Harris
Sites of Excitatory and Inhibitory Actions of Alcohols on Neuronal {alpha}2{beta}4 Nicotinic Acetylcholine Receptors
J. Pharmacol. Exp. Ther., October 1, 2003; 307(1): 42 - 52.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
Y. Zuo, J. Z. Yeh, and T. Narahashi
Dual Action of n-Butanol on Neuronal Nicotinic alpha 4beta 2 Acetylcholine Receptors
J. Pharmacol. Exp. Ther., March 1, 2003; 304(3): 1143 - 1152.
[Abstract] [Full Text] [PDF]

Home page
 Br J AnaesthHome page
J. P. Dilger
The effects of general anaesthetics on ligand-gated ion channels
Br. J. Anaesth., July 1, 2002; 89(1): 41 - 51.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2001 by the American Society for Pharmacology and Experimental Therapeutics