title: Tacrine and physostigmine block nicotinic receptors in Xenopus oocytes injected with Torpedo electroplaque membranes.
abstract: 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.
authors.affiliation: Departament de Biologia Cellular i Anatomia Patològica, Facultat de Medicina, Hospital de Bellvitge, Universitat de Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Cantí
authors.forename: E
authors.initials: E
authors.lastname: Bodas
authors.forename: J
authors.initials: J
authors.lastname: Marsal
authors.forename: C
authors.initials: C
authors.lastname: Solsona
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D009865:Oocytes / Q000378:metabolism; D010830:Physostigmine / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D013619:Tacrine / Q000494:pharmacology*; D014101:Torpedo; D014981:Xenopus
chemical_list: D002800:Cholinesterase Inhibitors; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D013619:Tacrine; D010830:Physostigmine