Okonjo, K. O. and Kuhlmann, Jurgen and Maelicke, Alfred
A second pathway of activation of the Torpedo acetylcholine receptor channel.
European Journal of Biochemistry.
We have studied the interaction of the reversible acetylcholine esterase inhibitor (-)physostigmine (D-eserine)
with the nicotinic acetylcholine receptor (nAChR) from Torpedo marmorata electric tissue by means of ligandinduced
ion flux into nAChR-rich membrane vesicles and of equilibrium binding. We find that (—)physostigmine
induces cation flux (and also binds to the receptor) even in the presence of saturating concentrations of antagonists
of acetylcholine, such as D-tubocurarine, a-bungarotoxin or antibody WF6, The direct action on the acetylcholine
receptor is not affected by removal of the methylcarbamate function from the drug and thus is not due to
carbamylation of the receptor. Antibodies FKl and benzoquinonium antagonize channel activation (and binding)
of eserine, suggesting that the eserine binding site(s) is separate from, but adjacent to, the acetylcholine binding
site at the receptor. In addition to the channel activating site(s) with an affinity of binding in the 50 nM range,
there exists a further class of low-affinity (K^ ~ mM) sites from which eserine acts as a direct blocker of the
acetylcholine-activatcd channel. Our results suggest the existence of a second pathway of activation of the nAChR
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