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J Pharmacol Exp Ther
2008 Nov 01;3272:529-37. doi: 10.1124/jpet.108.142943.
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Alpha-conotoxin Arenatus IB[V11L,V16D] [corrected] is a potent and selective antagonist at rat and human native alpha7 nicotinic acetylcholine receptors.
Innocent N
,
Livingstone PD
,
Hone A
,
Kimura A
,
Young T
,
Whiteaker P
,
McIntosh JM
,
Wonnacott S
.
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A recently developed alpha-conotoxin, alpha-conotoxin Arenatus IB-[V11L,V16D] (alpha-CtxArIB[V11L,V16D]) [corrected], is a potent and selective competitive antagonist at rat recombinant alpha7 nicotinic acetylcholine receptors (nAChRs), making it an attractive probe for this receptor subtype. alpha7 nAChRs are potential therapeutic targets that are widely expressed in both neuronal and non-neuronal tissues, where they are implicated in a variety of functions. In this study, we evaluate this toxin at rat and human native nAChRs. Functional alpha7 nAChR responses were evoked by choline plus the allosteric potentiator PNU-120596 [1-(5-chloro-2,4-dimethoxy-phenyl)-3-(5-methyl-isoxazol-3-yl)-urea] in rat PC12 cells and human SH-SY5Y cells loaded with calcium indicators. alpha-CtxArIB[V11L,V16D] specifically inhibited alpha7 nAChR-mediated increases in Ca2+ in PC12 cells. Responses to other stimuli, 5-I-A-85380 [5-iodo-3-(2(S)-azetidinylmethoxy)pyridine dihydrochloride], nicotine, or KCl, that did not activate alpha7 nAChRs were unaffected. Human alpha7 nAChRs were also sensitive to alpha-CtxArIB[V11L, V16D]; acetylcholine-evoked currents in Xenopus laevis oocytes expressing human alpha7 nAChRs were inhibited by alpha-CtxArIB[V11L,V16D] (IC(50), 3.4 nM) in a slowly reversible manner, with full recovery taking 15 min. This is consistent with the time course of recovery from blockade of rat alpha7 nAChRs in PC12 cells. alpha-CtxArIB[V11L,V16D] inhibited human native alpha7 nAChRs in SHSY5Y cells, activated by either choline or AR-R17779 [(2)-spiro[1-azabicyclo[2.2.2]octane-3,59-oxazolidin]-29-one] plus PNU-120596. Rat brain alpha7 nAChRs contribute to dopamine release from striatal minces; alpha-CtxArIB[V11L,V16D] (300 nM) selectively inhibited choline-evoked dopamine release without affecting responses evoked by nicotine that activates heteromeric nAChRs. This study establishes that alpha-CtxArIB[V11L,V16D] selectively inhibits human and rat native alpha7 nAChRs with comparable potency, making this a potentially useful antagonist for investigating alpha7 nAChR functions.
Alkondon,
Choline is a selective agonist of alpha7 nicotinic acetylcholine receptors in the rat brain neurons.
1997, Pubmed
Alkondon,
Choline is a selective agonist of alpha7 nicotinic acetylcholine receptors in the rat brain neurons.
1997,
Pubmed
Alkondon,
Subtype-specific inhibition of nicotinic acetylcholine receptors by choline: a regulatory pathway.
2006,
Pubmed
Baker,
Pharmacological properties of alpha 9 alpha 10 nicotinic acetylcholine receptors revealed by heterologous expression of subunit chimeras.
2004,
Pubmed
,
Xenbase
Barik,
Indirect modulation by alpha7 nicotinic acetylcholine receptors of noradrenaline release in rat hippocampal slices: interaction with glutamate and GABA systems and effect of nicotine withdrawal.
2006,
Pubmed
Biton,
SSR180711, a novel selective alpha7 nicotinic receptor partial agonist: (1) binding and functional profile.
2007,
Pubmed
,
Xenbase
Blumenthal,
Detection of functional nicotinic receptors blocked by alpha-bungarotoxin on PC12 cells and dependence of their expression on post-translational events.
1997,
Pubmed
Bschleipfer,
Expression and distribution of cholinergic receptors in the human urothelium.
2007,
Pubmed
Cartier,
A new alpha-conotoxin which targets alpha3beta2 nicotinic acetylcholine receptors.
1996,
Pubmed
,
Xenbase
Davies,
Characterisation of the binding of [3H]methyllycaconitine: a new radioligand for labelling alpha 7-type neuronal nicotinic acetylcholine receptors.
1999,
Pubmed
Decker,
Therapeutic potential of neuronal nicotinic acetylcholine receptor agonists as novel analgesics.
1999,
Pubmed
Dickinson,
Differential coupling of alpha7 and non-alpha7 nicotinic acetylcholine receptors to calcium-induced calcium release and voltage-operated calcium channels in PC12 cells.
2007,
Pubmed
Elgoyhen,
alpha10: a determinant of nicotinic cholinergic receptor function in mammalian vestibular and cochlear mechanosensory hair cells.
2001,
Pubmed
,
Xenbase
Grady,
The subtypes of nicotinic acetylcholine receptors on dopaminergic terminals of mouse striatum.
2007,
Pubmed
,
Xenbase
Grønlien,
Distinct profiles of alpha7 nAChR positive allosteric modulation revealed by structurally diverse chemotypes.
2007,
Pubmed
,
Xenbase
Hajós,
The selective alpha7 nicotinic acetylcholine receptor agonist PNU-282987 [N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide hydrochloride] enhances GABAergic synaptic activity in brain slices and restores auditory gating deficits in anesthetized rats.
2005,
Pubmed
Henderson,
Nerve growth factor increases nicotinic ACh receptor gene expression and current density in wild-type and protein kinase A-deficient PC12 cells.
1994,
Pubmed
Hurst,
A novel positive allosteric modulator of the alpha7 neuronal nicotinic acetylcholine receptor: in vitro and in vivo characterization.
2005,
Pubmed
,
Xenbase
Jensen,
Neuronal nicotinic acetylcholine receptors: structural revelations, target identifications, and therapeutic inspirations.
2005,
Pubmed
Kaiser,
alpha-bungarotoxin-sensitive nicotinic receptors indirectly modulate [(3)H]dopamine release in rat striatal slices via glutamate release.
2000,
Pubmed
Klink,
Molecular and physiological diversity of nicotinic acetylcholine receptors in the midbrain dopaminergic nuclei.
2001,
Pubmed
Levin,
Nicotinic effects on cognitive function: behavioral characterization, pharmacological specification, and anatomic localization.
2006,
Pubmed
Lips,
Coexpression and spatial association of nicotinic acetylcholine receptor subunits alpha7 and alpha10 in rat sympathetic neurons.
2006,
Pubmed
Lukas,
Characterization of Nicotinic Acetylcholine Receptors Expressed by Cells of the SH-SY5Y Human Neuroblastoma Clonal Line.
1993,
Pubmed
Marks,
Deletion of the alpha7, beta2, or beta4 nicotinic receptor subunit genes identifies highly expressed subtypes with relatively low affinity for [3H]epibatidine.
2006,
Pubmed
Mazurov,
Selective alpha7 nicotinic acetylcholine receptor ligands.
2006,
Pubmed
McIntosh,
Conus peptides targeted to specific nicotinic acetylcholine receptor subtypes.
1999,
Pubmed
McKay,
Regulation of synaptic transmission and plasticity by neuronal nicotinic acetylcholine receptors.
2007,
Pubmed
Mogg,
Methyllycaconitine is a potent antagonist of alpha-conotoxin-MII-sensitive presynaptic nicotinic acetylcholine receptors in rat striatum.
2002,
Pubmed
Nicke,
Alpha-conotoxins as tools for the elucidation of structure and function of neuronal nicotinic acetylcholine receptor subtypes.
2004,
Pubmed
Peng,
Human alpha 7 acetylcholine receptor: cloning of the alpha 7 subunit from the SH-SY5Y cell line and determination of pharmacological properties of native receptors and functional alpha 7 homomers expressed in Xenopus oocytes.
1994,
Pubmed
,
Xenbase
Puttfarcken,
Characterization of nicotinic acetylcholine receptor-mediated [(3)H]-dopamine release from rat cortex and striatum.
2000,
Pubmed
Ridley,
Differential effects of chronic drug treatment on alpha3* and alpha7 nicotinic receptor binding sites, in hippocampal neurones and SH-SY5Y cells.
2001,
Pubmed
Timmermann,
An allosteric modulator of the alpha7 nicotinic acetylcholine receptor possessing cognition-enhancing properties in vivo.
2007,
Pubmed
,
Xenbase
Wang,
Assembly of human neuronal nicotinic receptor alpha5 subunits with alpha3, beta2, and beta4 subunits.
1996,
Pubmed
,
Xenbase
Whiteaker,
Discovery, synthesis, and structure activity of a highly selective alpha7 nicotinic acetylcholine receptor antagonist.
2007,
Pubmed
,
Xenbase
Whiteaker,
Identification of a novel nicotinic binding site in mouse brain using [(125)I]-epibatidine.
2000,
Pubmed
Wilens,
Neuronal nicotinic receptor agonists for the treatment of attention-deficit/hyperactivity disorder: focus on cognition.
2007,
Pubmed
Wyllie,
Taking the time to study competitive antagonism.
2007,
Pubmed
Young,
Species selectivity of a nicotinic acetylcholine receptor agonist is conferred by two adjacent extracellular beta4 amino acids that are implicated in the coupling of binding to channel gating.
2007,
Pubmed
de Jonge,
The alpha7 nicotinic acetylcholine receptor as a pharmacological target for inflammation.
2007,
Pubmed
