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We studied allosteric potentiation of rat alpha3beta2 neuronal nicotinic acetylcholine receptors (nAChRs) by the anthelmintic compound morantel. Macroscopic currents evoked by acetylcholine (ACh) from nAChRs expressed in Xenopus laevis oocytes increase up to 8-fold in the presence of low concentrations of morantel (< or =10 microM); the magnitude of the potentiation depends on both agonist and modulator concentrations. It is noteworthy that the potentiated currents exceed the maximum currents achieved by saturating (millimolar) concentrations of agonist. Studies of macroscopic currents elicited by prolonged drug applications (100-300 s) indicate that morantel does not increase alpha3beta2 receptor activity by reducing slow (> or =1 s) desensitization. Instead, using outside-out patch-clamp recordings, we demonstrate that morantel increases the frequency of single-channel openings and alters the bursting characteristics of the openings in a manner consistent with enhanced channel gating; these results quantitatively explain the macroscopic current potentiation. Morantel is a very weak agonist alone, but we show that the classic competitive antagonist dihydro-beta-erythroidine inhibits morantel-evoked currents noncompetitively, indicating that morantel does not bind to the canonical ACh binding sites.
Akk,
Galantamine activates muscle-type nicotinic acetylcholine receptors without binding to the acetylcholine-binding site.
2005, Pubmed
Akk,
Galantamine activates muscle-type nicotinic acetylcholine receptors without binding to the acetylcholine-binding site.
2005,
Pubmed Berrettini,
Pharmacotherapy and pharmacogenetics of nicotine dependence.
2005,
Pubmed Brejc,
Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors.
2001,
Pubmed Broad,
Identification and pharmacological profile of a new class of selective nicotinic acetylcholine receptor potentiators.
2006,
Pubmed
,
Xenbase Cachelin,
Unusual pharmacology of (+)-tubocurarine with rat neuronal nicotinic acetylcholine receptors containing beta 4 subunits.
1994,
Pubmed
,
Xenbase Colquhoun,
Binding, gating, affinity and efficacy: the interpretation of structure-activity relationships for agonists and of the effects of mutating receptors.
1998,
Pubmed Colquhoun,
Activation of ion channels in the frog end-plate by high concentrations of acetylcholine.
1988,
Pubmed Colquhoun,
Fast events in single-channel currents activated by acetylcholine and its analogues at the frog muscle end-plate.
1985,
Pubmed Cooper,
Pharmacology of the nicotinic acetylcholine receptor from fetal rat muscle expressed in Xenopus oocytes.
1996,
Pubmed
,
Xenbase Downing,
Benzodiazepine modulation of partial agonist efficacy and spontaneously active GABA(A) receptors supports an allosteric model of modulation.
2005,
Pubmed Fenster,
Influence of subunit composition on desensitization of neuronal acetylcholine receptors at low concentrations of nicotine.
1997,
Pubmed
,
Xenbase Ferreri,
Cognitive dysfunctions in schizophrenia: potential benefits of cholinesterase inhibitor adjunctive therapy.
2006,
Pubmed Fleck,
Molecular actions of (S)-desmethylzopiclone (SEP-174559), an anxiolytic metabolite of zopiclone.
2002,
Pubmed Giniatullin,
Desensitization of nicotinic ACh receptors: shaping cholinergic signaling.
2005,
Pubmed Hansen,
Galanthamine and non-competitive inhibitor binding to ACh-binding protein: evidence for a binding site on non-alpha-subunit interfaces of heteromeric neuronal nicotinic receptors.
2007,
Pubmed Harvey,
Determinants of competitive antagonist sensitivity on neuronal nicotinic receptor beta subunits.
1996,
Pubmed
,
Xenbase Hevers,
The diversity of GABAA receptors. Pharmacological and electrophysiological properties of GABAA channel subtypes.
1998,
Pubmed Hogg,
Partial agonists as therapeutic agents at neuronal nicotinic acetylcholine receptors.
2007,
Pubmed Hsiao,
Determinants of zinc potentiation on the alpha4 subunit of neuronal nicotinic receptors.
2006,
Pubmed
,
Xenbase Hsiao,
Zinc potentiates neuronal nicotinic receptors by increasing burst duration.
2008,
Pubmed
,
Xenbase Hurst,
A novel positive allosteric modulator of the alpha7 neuronal nicotinic acetylcholine receptor: in vitro and in vivo characterization.
2005,
Pubmed
,
Xenbase Lee,
Principal pathway coupling agonist binding to channel gating in nicotinic receptors.
2005,
Pubmed Lee,
Invariant aspartic Acid in muscle nicotinic receptor contributes selectively to the kinetics of agonist binding.
2004,
Pubmed Levandoski,
The anthelmintic levamisole is an allosteric modulator of human neuronal nicotinic acetylcholine receptors.
2003,
Pubmed
,
Xenbase Lyford,
Agonist-induced conformational changes in the extracellular domain of alpha 7 nicotinic acetylcholine receptors.
2003,
Pubmed
,
Xenbase Maelicke,
Allosteric modulation of nicotinic acetylcholine receptors as a treatment strategy for Alzheimer's disease.
2000,
Pubmed Martin,
Modes of action of anthelmintic drugs.
1997,
Pubmed Mathie,
Conductance and kinetic properties of single nicotinic acetylcholine receptor channels in rat sympathetic neurones.
1991,
Pubmed Mitra,
Structural dynamics of the M4 transmembrane segment during acetylcholine receptor gating.
2004,
Pubmed Ohno,
Congenital myasthenic syndrome caused by decreased agonist binding affinity due to a mutation in the acetylcholine receptor epsilon subunit.
1996,
Pubmed Papke,
The role of the beta 4-subunit in determining the kinetic properties of rat neuronal nicotinic acetylcholine alpha 3-receptors.
1991,
Pubmed
,
Xenbase Pereira,
Physostigmine and galanthamine: probes for a novel binding site on the alpha 4 beta 2 subtype of neuronal nicotinic acetylcholine receptors stably expressed in fibroblast cells.
1994,
Pubmed Pereira,
Identification and functional characterization of a new agonist site on nicotinic acetylcholine receptors of cultured hippocampal neurons.
1993,
Pubmed Rang,
Drugs and ionic channels: mechanisms and implications.
1981,
Pubmed Rayes,
Molecular basis of the differential sensitivity of nematode and mammalian muscle to the anthelmintic agent levamisole.
2004,
Pubmed Rogers,
Benzodiazepine and beta-carboline regulation of single GABAA receptor channels of mouse spinal neurones in culture.
1994,
Pubmed Schrattenholz,
Agonist responses of neuronal nicotinic acetylcholine receptors are potentiated by a novel class of allosterically acting ligands.
1996,
Pubmed Sine,
The nicotinic receptor ligand binding domain.
2002,
Pubmed Sine,
Activation of Torpedo acetylcholine receptors expressed in mouse fibroblasts. Single channel current kinetics reveal distinct agonist binding affinities.
1990,
Pubmed Singhal,
Antipsychotic clozapine inhibits the function of alpha7-nicotinic acetylcholine receptors.
2007,
Pubmed
,
Xenbase Smulders,
Cholinergic drugs potentiate human nicotinic alpha4beta2 acetylcholine receptors by a competitive mechanism.
2005,
Pubmed
,
Xenbase Unwin,
Refined structure of the nicotinic acetylcholine receptor at 4A resolution.
2005,
Pubmed Zhang,
Activation of recombinant mouse acetylcholine receptors by acetylcholine, carbamylcholine and tetramethylammonium.
1995,
Pubmed
,
Xenbase Zwart,
Competitive potentiation of acetylcholine effects on neuronal nicotinic receptors by acetylcholinesterase-inhibiting drugs.
2000,
Pubmed
,
Xenbase Zwart,
Potentiation and inhibition of neuronal alpha4beta4 nicotinic acetylcholine receptors by choline.
2000,
Pubmed
,
Xenbase
