0000000000248849

AUTHOR

Alexander Storch

showing 4 related works from this author

Noncompetitive agonism at nicotinic acetylcholine receptors; functional significance for CNS signal transduction.

1995

The alkaloids (-)physostigmine (Phy), galanthamine (Gal) and codeine (Cod), and several derivatives and homologous compounds, can act as noncompetitive agonists (NCA) of nicotinic acetylcholine receptors (nAChR) from Torpedo electrocytes, frog and mammalian muscle cells, clonal rat pheochromocytoma cells, cultured hippocampal neurons and several ectopic expression systems, by interacting with a binding site on the alpha-subunits of these nAChRs that is insensitive to the natural transmitter, acetylcholine (ACh), and ACh-competitive agonists and antagonists. Several endogenous ligands, including opioid-type compounds, can also act via this site, albeit at higher concentrations than is typica…

Central Nervous SystemPharmacologyReceptors NicotinicLigandsBiochemistrylaw.inventionEvolution MolecularlawMuscarinic acetylcholine receptormedicineAnimalsHumansNicotinic AgonistsBinding siteReceptorMolecular BiologyAcetylcholine receptorBinding SitesMolecular StructureChemistryCell BiologyAcetylcholineCell biologyNicotinic agonistnervous systemSignal transductionAcetylcholineTorpedomedicine.drugSignal TransductionJournal of receptor and signal transduction research
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Stable expression in HEK-293 cells of the rat alpha3/beta4 subtype of neuronal nicotinic acetylcholine receptor.

1996

The alpha3/beta4 subtype of neuronal nicotinic acetylcholine receptor (nAChR) was stably expressed in human embryonic kidney (HEK) 293 cells that co-expressed a voltage-gated Ca2+ channel. alpha3/beta4-nAChR-expressing clones were identified using the fura-2 Ca2+ imaging technique, and were further characterised by single-cell and whole-cell patch-clamp studies. Acetylcholine (ACh) induced fast activating currents which showed desensitisation and inward rectification. The conductance of the ACh-activated channel was 29 pS. The order of potency of the nicotinic agonists tested was cytisine approximately = nicotine > acetylcholine. The EC50 value for ACh was 145 microM; the Hill coefficient w…

Stable expressionPatch-Clamp Techniquesα3/β4 nAChRBiophysicsNicotinic AntagonistsPharmacologyReceptors NicotinicTransfectionBiochemistryCell LineGanglionic nAChRCa2+ imagingGanglion type nicotinic receptorStructural BiologyMuscarinic acetylcholine receptorGeneticsmedicineAnimalsHumansNicotinic AgonistsNicotinic AntagonistHEK cellMolecular BiologyNeuronsurogenital systemChemistryMuscarinic acetylcholine receptor M3Cell BiologyAcetylcholineRecombinant ProteinsRatsNicotinic acetylcholine receptorNicotinic agonistCalciumCalcium ChannelsAlpha-4 beta-2 nicotinic receptorAcetylcholinemedicine.drugFEBS letters
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Introductory Lecture: Allosteric Modulation of Torpedo Nicotinic Acetylcholine Receptor Ion Channel Activity by Noncompetitive Agonists

1997

AbstractSimilar to other neuroreceptors of the vertebrate central nervous system, the nicotinic acetylcholine receptor (nAChR) is subject to modulatory control by allosterically acting ligands. Of particular interest in this regard are allosteric ligands that enhance the sensitivity of the receptor to its natural agonist acetylcholine (ACh), as such ligands could be useful as drugs in diseases associated with impaired nicotinic neurotransmission. Here we discuss the action of a novel class of nAChR ligands which act as allosterically potentiating ligands (APL) on the nicotinic responses induced by ACh and competitive agonists. In addition, APLs also act as noncompetitive agonists of very lo…

Agonistmedicine.drug_classChemistryAllosteric regulationCell BiologyPharmacologyBiochemistryNicotinic acetylcholine receptorNicotinic agonistGanglion type nicotinic receptorMuscarinic acetylcholine receptormedicineAlpha-4 beta-2 nicotinic receptorMolecular BiologyAcetylcholinemedicine.drugJournal of Receptors and Signal Transduction
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Physostigmine and Neuromuscular Transmission

1993

Single channel studies carried out in cultured rat myoballs and cultured hippocampal neurons, and ion flux studies performed on Torpedo electrocyte membrane vesicles, showed that physostigmine (Phy), a well-established acetylcholinesterase inhibitor, interacts directly with nicotinic acetylcholine receptors (nAChR). Low concentrations (0.1 microM) of Phy activate the receptor integral channel, whereas higher concentrations blocked the channel in its opened state. In contrast to channel activation by acetylcholine (ACh) and classical cholinergic agonists, however, Phy was capable of activating the nAChR channel even when the ACh binding sites were blocked by competitive antagonists, such as …

PhysostigmineMolecular Sequence DataNeuromuscular JunctionNeuromuscular transmissionIn Vitro TechniquesReceptors NicotinicTorpedoHippocampusSynaptic TransmissionGeneral Biochemistry Genetics and Molecular BiologyNeuromuscular junctionHistory and Philosophy of SciencemedicineAnimalsAmino Acid SequencePatch clampBinding siteCells CulturedAcetylcholine receptorBinding SitesChemistryGeneral NeuroscienceAcetylcholineRatsQuaternary Ammonium CompoundsNicotinic agonistmedicine.anatomical_structureBiophysicsCholinergicIon Channel GatingNeuroscienceAcetylcholinemedicine.drugAnnals of the New York Academy of Sciences
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