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 Lurtz, M. M.
Right arrow Articles by Pedersen, S. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lurtz, M. M.
Right arrow Articles by Pedersen, S. E.

Vol. 55, Issue 1, 159-167, January 1999

Aminotriarylmethane Dyes Are High-Affinity Noncompetitive Antagonists of the Nicotinic Acetylcholine Receptor

Monica M. Lurtz1 and Steen E. Pedersen

Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas

A series of aminotriarylmethane dyes were examined for binding to the nicotinic acetylcholine receptor (AChR) from Torpedo californica. Several compounds were found to bind to the noncompetitive antagonist site of the AChR as demonstrated by inhibition of [3H]phencyclidine binding; apparent KD values ranged from 50 nM to >100 µM. One dye with high affinity, crystal violet, revealed a greater than 200-fold fluorescence enhancement upon binding the AChR. Using fluorescence to measure binding, we determined that one crystal violet bound per receptor with a dissociation constant of 100 nM; in the presence of the agonist carbamylcholine this value decreased to 10 nM. The KD for [3H]acetylcholine binding likewise was decreased in the presence of crystal violet. These results are consistent with preferential binding of crystal violet to the desensitized conformation of the AChR. Crystal violet binding blocked agonist-induced 22Na ion efflux from AChR-rich vesicles. It is concluded that crystal violet and other dyes of similar structure bind to the high-affinity noncompetitive antagonist site of the AChR associated with the channel lumen. Because of their optical properties, crystal violet and several of the other homologous dyes are likely to be useful ligands for further characterization of the AChR channel. Structure-activity comparison of the various dyes suggests the importance of nonquaternary nitrogens in binding the pore. Additional steric bulk on amines or at meta positions increase or have neutral effect on affinity, suggesting that steric considerations alone do not limit high affinity for the binding site.

Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
G. A. F. Nievas, F. J. Barrantes, and S. S. Antollini
Modulation of Nicotinic Acetylcholine Receptor Conformational State by Free Fatty Acids and Steroids
J. Biol. Chem., August 1, 2008; 283(31): 21478 - 21486.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
R. H. Meltzer, M. M. Lurtz, T. G. Wensel, and S. E. Pedersen
Nicotinic Acetylcholine Receptor Channel Electrostatics Determined by Diffusion-Enhanced Luminescence Energy Transfer
Biophys. J., August 15, 2006; 91(4): 1315 - 1324.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
R. H. Meltzer, W. Vila-Carriles, J. O. Ebalunode, J. M. Briggs, and S. E. Pedersen
Computed Pore Potentials of the Nicotinic Acetylcholine Receptor
Biophys. J., August 15, 2006; 91(4): 1325 - 1335.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
H. R. Arias, E. A. McCardy, and M. P. Blanton
Characterization of the Dizocilpine Binding Site on the Nicotinic Acetylcholine Receptor
Mol. Pharmacol., April 16, 2001; 59(5): 1051 - 1060.
[Abstract] [Full Text]

Home page
 Mol. Pharmacol.Home page
R. E. Middleton, N. P. Strnad, and J. B. Cohen
Photoaffinity Labeling the Torpedo Nicotinic Acetylcholine Receptor with [3H]Tetracaine, a Nondesensitizing Noncompetitive Antagonist
Mol. Pharmacol., August 1, 1999; 56(2): 290 - 299.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
R. V. L. Papineni, J. U. Sanchez, K. Baksi, I. U. Willcockson, and S. E. Pedersen
Site-specific Charge Interactions of alpha -Conotoxin MI with the Nicotinic Acetylcholine Receptor
J. Biol. Chem., June 22, 2001; 276(26): 23589 - 23598.
[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 © 1999 by the American Society for Pharmacology and Experimental Therapeutics