Tacrine and physostigmine block nicotinic receptors in Xenopus oocytes injected with Torpedo electroplaque membranes.

Tacrine and physostigmine were tested for direct nicotinic actions on Xenopus oocytes microinjected with Torpedo electroplaque membranes. In this preparation, responses to acetylcholine arise 6-8 h after microinjection, due to the incorporation of nicotinic receptors into the plasma membrane by a process not involving protein synthesis. Currents elicited by acetylcholine (100-1000 microM) were recorded by two-electrode voltage clamping. Tacrine (1-1000 microM) and physostigmine (1-100 microM) exerted a potent, reversible block of the nicotinic receptors. The concentration-dependence curves fitted simple hyperbolas, suggesting a stoichiometry of 1:1 in the drug-channel interactions. Currents elicited by the highest acetylcholine concentration were inhibited by tacrine with maximal affinity, indicating an action at a site other than the ligand-binding domain. Inhibition was reduced at depolarising potentials, which is consistent with a preferential interaction with the ligand-bound form of the receptor. Blockade by tacrine or physostigmine was accompanied by a concentration-dependent slowing of the desensitisation, resembling the action of local anaesthetics. These results could indicate a modulatory effect of these drugs on neurosecretion through nicotinic receptors.