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Biochem Pharmacol
2012 Aug 01;843:352-65. doi: 10.1016/j.bcp.2012.04.022.
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The nicotinic acetylcholine receptors of zebrafish and an evaluation of pharmacological tools used for their study.
Papke RL
,
Ono F
,
Stokes C
,
Urban JM
,
Boyd RT
.
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Zebrafish (Danio rerio) have been used to study multiple effects of nicotine, for example on cognition, locomotion, and stress responses, relying on the assumption that pharmacological tools will operate similarly upon molecular substrates in the fish and mammalian systems. We have cloned the zebrafish nicotinic acetylcholine receptor (nAChR) subunits and expressed key nAChR subtypes in Xenopus oocytes including neuronal (α4β2, α2β2, α3β4, and α7) and muscle (α1β1(b)ɛδ) nAChR. Consistent with studies of mammalian nAChR, nicotine was relatively inactive on muscle-type receptors, having both low potency and efficacy. It had high efficacy but low potency for α7 receptors, and the best potency and good efficacy for α4β2 receptors. Cytisine, a key lead compound for the development of smoking cessation agents, is a full agonist for both mammalian α7 and α3β4 receptors, but a full agonist only for the fish α7, with surprisingly low efficacy for α3β4. The efficacy of cytisine for α4β2 was somewhat greater than typically reported for mammalian α4β2. The ganglionic blocker mecamylamine was most potent for blocking α3β4 receptors, least potent for α7, and roughly equipotent for the muscle receptors and the β2-containing nAChR. However, the block of β2-containing receptors was slowly reversible, consistent with effective targeting of these CNS-type receptors in vivo. Three prototypical α7-selective agonists, choline, tropane, and 4OH-GTS-21, were tested, and these agents were observed to activate both fish α7 and α4β2 nAChR. Our data therefore indicate that while some pharmacological tools used in zebrafish may function as expected, others will not.
Ackerman,
Cloning and spatiotemporal expression of zebrafish neuronal nicotinic acetylcholine receptor alpha 6 and alpha 4 subunit RNAs.
2009, Pubmed
Ackerman,
Cloning and spatiotemporal expression of zebrafish neuronal nicotinic acetylcholine receptor alpha 6 and alpha 4 subunit RNAs.
2009,
Pubmed
Andreasen,
Antidepressant-like effects of nicotinic acetylcholine receptor antagonists, but not agonists, in the mouse forced swim and mouse tail suspension tests.
2009,
Pubmed
Bencan,
The role of alpha7 and alpha4beta2 nicotinic receptors in the nicotine-induced anxiolytic effect in zebrafish.
2008,
Pubmed
Brejc,
Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors.
2001,
Pubmed
Clemente,
Cholinergic elements in the zebrafish central nervous system: Histochemical and immunohistochemical analysis.
2004,
Pubmed
Colwill,
Imaging escape and avoidance behavior in zebrafish larvae.
2011,
Pubmed
David,
Biochemical and functional properties of distinct nicotinic acetylcholine receptors in the superior cervical ganglion of mice with targeted deletions of nAChR subunit genes.
2010,
Pubmed
,
Xenbase
Delvecchio,
The zebrafish: a powerful platform for in vivo, HTS drug discovery.
2011,
Pubmed
Eddins,
Nicotine effects on learning in zebrafish: the role of dopaminergic systems.
2009,
Pubmed
Epley,
A modified acetylcholine receptor delta-subunit enables a null mutant to survive beyond sexual maturation.
2008,
Pubmed
Figl,
Regions of beta 4.beta 2 subunit chimeras that contribute to the agonist selectivity of neuronal nicotinic receptors.
1992,
Pubmed
,
Xenbase
Francis,
Sensitivity to voltage-independent inhibition determined by pore-lining region of the acetylcholine receptor.
1998,
Pubmed
,
Xenbase
Gotti,
Brain nicotinic acetylcholine receptors: native subtypes and their relevance.
2006,
Pubmed
Goujon,
A new bioinformatics analysis tools framework at EMBL-EBI.
2010,
Pubmed
Heinemann,
The brain nicotinic acetylcholine receptor gene family.
1990,
Pubmed
Hoda,
Pleiotropic functional effects of the first epilepsy-associated mutation in the human CHRNA2 gene.
2009,
Pubmed
,
Xenbase
Horenstein,
Multiple pharmacophores for the selective activation of nicotinic alpha7-type acetylcholine receptors.
2008,
Pubmed
,
Xenbase
Ikenaga,
Formation of the spinal network in zebrafish determined by domain-specific pax genes.
2011,
Pubmed
Kuryatov,
Roles of accessory subunits in alpha4beta2(*) nicotinic receptors.
2008,
Pubmed
Langheinrich,
Zebrafish: a new model on the pharmaceutical catwalk.
2003,
Pubmed
Larkin,
Clustal W and Clustal X version 2.0.
2007,
Pubmed
Leiser,
A cog in cognition: how the alpha 7 nicotinic acetylcholine receptor is geared towards improving cognitive deficits.
2009,
Pubmed
Levin,
Nicotinic involvement in memory function in zebrafish.
2004,
Pubmed
Levin,
Timing of nicotine effects on learning in zebrafish.
2006,
Pubmed
Levin,
Anxiolytic effects of nicotine in zebrafish.
2007,
Pubmed
Levin,
Zebrafish assessment of cognitive improvement and anxiolysis: filling the gap between in vitro and rodent models for drug development.
2011,
Pubmed
Li,
The neuronal nicotinic alpha4beta2 receptor has a high maximal probability of being open.
2010,
Pubmed
Matta,
Guidelines on nicotine dose selection for in vivo research.
2007,
Pubmed
McKinley,
Neuroprotection of MPTP-induced toxicity in zebrafish dopaminergic neurons.
2005,
Pubmed
Meyer,
From 2R to 3R: evidence for a fish-specific genome duplication (FSGD).
2005,
Pubmed
Mineur,
Cytisine-based nicotinic partial agonists as novel antidepressant compounds.
2009,
Pubmed
,
Xenbase
Mongeon,
An acetylcholine receptor lacking both γ and ε subunits mediates transmission in zebrafish slow muscle synapses.
2011,
Pubmed
,
Xenbase
Papke,
Comparative pharmacology of rat and human alpha7 nAChR conducted with net charge analysis.
2002,
Pubmed
,
Xenbase
Papke,
Partial agonist properties of cytisine on neuronal nicotinic receptors containing the beta 2 subunit.
1994,
Pubmed
,
Xenbase
Papke,
Tricks of perspective: insights and limitations to the study of macroscopic currents for the analysis of nAChR activation and desensitization.
2010,
Pubmed
,
Xenbase
Papke,
Activation and inhibition of mouse muscle and neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes.
2010,
Pubmed
,
Xenbase
Papke,
Electrophysiological perspectives on the therapeutic use of nicotinic acetylcholine receptor partial agonists.
2011,
Pubmed
,
Xenbase
Pavlov,
Selective alpha7-nicotinic acetylcholine receptor agonist GTS-21 improves survival in murine endotoxemia and severe sepsis.
2007,
Pubmed
Petersen,
SignalP 4.0: discriminating signal peptides from transmembrane regions.
2011,
Pubmed
Picciotto,
It is not "either/or": activation and desensitization of nicotinic acetylcholine receptors both contribute to behaviors related to nicotine addiction and mood.
2008,
Pubmed
Picciotto,
Neuronal nicotinic acetylcholine receptor subunit knockout mice: physiological and behavioral phenotypes and possible clinical implications.
2001,
Pubmed
Role,
Nicotinic receptors in the development and modulation of CNS synapses.
1996,
Pubmed
Roncarati,
Procognitive and neuroprotective activity of a novel alpha7 nicotinic acetylcholine receptor agonist for treatment of neurodegenerative and cognitive disorders.
2009,
Pubmed
Webster,
Antagonist activities of mecamylamine and nicotine show reciprocal dependence on beta subunit sequence in the second transmembrane domain.
1999,
Pubmed
,
Xenbase
Zirger,
Cloning and expression of zebrafish neuronal nicotinic acetylcholine receptors.
2003,
Pubmed
