6533b831fe1ef96bd1298736
RESEARCH PRODUCT
Biochemical Characterization of a Novel Channel-Activating Site on Nicotinic Acetylcholine Receptors
André SchrattenholzEdna F. R. PereiraBernd SchröderJürgen KuhlmannAlfred MaelickeThomas CobanEdson X. AlbuquerqueKehinde O. Okonjosubject
PharmacologyPhotoaffinity labelingChemistryPhysostigmineMolecular Sequence DataIn Vitro TechniquesReceptors NicotinicTorpedoIon ChannelsAcetylcholine bindingNicotinic acetylcholine receptorNicotinic agonistnervous systemBiochemistrymedicineAnimalsChannel blockerAmino Acid SequenceBinding siteAcetylcholineAcetylcholine receptormedicine.drugdescription
We have studied the interaction of the reversible acetylcholine esterase inhibitor (-)physostigmine and several structurally related compounds with the nicotinic acetylcholine receptor (nAChR) from Torpedo marmorata electric tissue by means of ligand-induced ion flux into nAChR-rich membrane vesicles, direct binding studies and photoaffinity labeling. (-)Physostigmine acts as a channel-activating ligand at low concentrations and as a direct channel blocker at elevated concentrations. Channel activation is not inhibited by desensitizing concentrations of ACh or ACh-competitive ligands (including alpha-bungarotoxin and D-tubocurarine) but is inhibited by antibody FK1 and several other compounds. From photoaffinity labeling using tritiated physostigmine and mapping of the epitope for the Phy-competitive antibody FK1, the binding site for physostigmine is located within the alpha-subunit of the Torpedo nAChR and is distinct from the acetylcholine binding site. Our data suggest a second pathway of nAChR channel activation that may function physiologically as an allosteric control of receptor activity.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 1993-01-01 | Journal of Receptor Research |