John Daly’s Compound, Epibatidine, Facilitates Identification of Nicotinic Receptor Subtypes
Michael J. Marks,Duncan Laverty,Paul Whiteaker,Outi Salminen,Sharon R. Grady,J. Michael McIntosh,Allan C. Collins +6 more
TLDR
The diversity of nicotinic acetylcholine receptor (nAChR) subtypes was explored by measuring the effects of gene deletion and pharmacological diversity of epibatidine binding sites in mouse brain, indicating unique functional roles.Abstract:
The diversity of nicotinic acetylcholine receptor (nAChR) subtypes was explored by measuring the effects of gene deletion and pharmacological diversity of epibatidine binding sites in mouse brain. All epibatidine binding sites require expression of either the α7, β2, or β4 subunit. In agreement with general belief, the α4β2*-nAChR and α7-nAChR subtypes are major components of the epibatidine binding sites. α4β2*-nAChR sites account for approximately 70% of total high- and low-affinity epibatidine binding sites, while α7-nAChR accounts for 16% of the total sites all of which have lower affinity for epibatidine. The other subtypes are structurally diverse. Although these minor subtypes account for only 14% of total binding in whole brain, they are expressed at relatively high concentrations in specific brain areas indicating unique functional roles.read more
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Aversion to Nicotine Is Regulated by the Balanced Activity of β4 and α5 Nicotinic Receptor Subunits in the Medial Habenula
Silke Frahm,Marta A. Ślimak,Leiron Ferrarese,Julio Santos-Torres,Beatriz Antolin-Fontes,Sebastian Auer,Sergey Yu. Filkin,Stéphanie Pons,Jean-Fred Fontaine,Victor I. Tsetlin,Uwe Maskos,Uwe Maskos,Inés Ibañez-Tallon +12 more
TL;DR: This study provides insights into α3β4α5 receptor-mediated mechanisms contributing to nicotine consumption, and identifies the MHb as a critical element in the circuitry controlling nicotine-dependent phenotypes.
Journal ArticleDOI
Acetylcholine Receptor (AChR) α5 Subunit Variant Associated with Risk for Nicotine Dependence and Lung Cancer Reduces (α4β2)2α5 AChR Function
TL;DR: It is reported that α5 Asn 398 lowers Ca2+ permeability and increases short-term desensitization in (α4β2)2 α5 but not in ( α3β4)2α5 or (α3β2), which suggests that a positive allosteric modulator would augment nicotine replacement therapy for those with this risk variant.
Journal ArticleDOI
Sequestered defensive toxins in tetrapod vertebrates: principles, patterns, and prospects for future studies
Alan H. Savitzky,Akira Mori,Deborah A. Hutchinson,Ralph A. Saporito,Gordon M. Burghardt,Harvey B. Lillywhite,Jerrold Meinwald +6 more
TL;DR: The number of described cases of defensive sequestration in tetrapod vertebrates has increased recently and includes diverse lineages of amphibians and reptiles (including birds); it remains uncertain whether any sequestered toxins of tetrapods bioaccumulate across multiple trophic levels, but multitrophic accumulation seems especially likely.
Journal ArticleDOI
An autoradiographic survey of mouse brain nicotinic acetylcholine receptors defined by null mutants
TL;DR: These results confirm and extend previously published evaluations of the effect of nAChR gene deletion and help to define the nA ChR subtypes measurable by ligand binding.
Journal ArticleDOI
Low Dose Nicotine and Antagonism of β2 Subunit Containing Nicotinic Acetylcholine Receptors Have Similar Effects on Affective Behavior in Mice
TL;DR: Evidence that inactivation of β2*nAChRs reduces fear-like and anxiety-like behavior in rodents is provided and it is suggested that smokers may be motivated to smoke in part to desensitize their nAChR receptors.
References
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Nicotinic binding in rat brain: autoradiographic comparison of [3H]acetylcholine, [3H]nicotine, and [125I]-alpha-bungarotoxin
TL;DR: Detailed maps of high affinity agonist labeling are produced, with highest densities in the interpeduncular nucleus, most thalamic nuclei, superior colliculus, medial habenula, presubiculum, cerebral cortex (layers I and III/IV), and the substantia nigra pars compacta/ventral tegmental area.
Journal ArticleDOI
Abnormal avoidance learning in mice lacking functional high-affinity nicotine receptor in the brain.
Marina R. Picciotto,Michele Zoli,Clément Léna,Alain Bessis,Yvan Lallemand,Nicolas LeNovère,Pierre Vincent,Emilio Merlo Pich,Philippe Brulet,Jean-Pierre Changeux +9 more
TL;DR: It is reported here that high-affinity binding sites for nicotine are absent from the brains of mice homozygous for the β2-subunit mutation, and electrophysiological recording from brain slices reveals that thalamic neurons from these mice do not respond to nicotine application.
Journal ArticleDOI
Reduced antinociception in mice lacking neuronal nicotinic receptor subunits
Lisa M. Marubio,Maria del Mar Arroyo-Jimenez,Matilde Cordero-Erausquin,Clément Léna,Nicolas Le Novère,Alban de Kerchove d'Exaerde,Monique Huchet,M. Imad Damaj,M. Imad Damaj,Jean-Pierre Changeux +9 more
TL;DR: It is shown that the homozygous α4−/− mice no longer express high-affinity [ 3H]nicotine and [3H]epibatidine binding sites throughout the brain, and patch-clamp recordings reveal that raphe magnus and thalamic neurons no longer respond to nicotine.
Journal ArticleDOI
Subunit composition of functional nicotinic receptors in dopaminergic neurons investigated with knock-out mice
Nicolas Champtiaux,Cecilia Gotti,Matilde Cordero-Erausquin,Denis J. David,Cédric Przybylski,Clément Léna,Francesco Clementi,Milena Moretti,Francesco M. Rossi,Nicolas Le Novère,J. Michael McIntosh,Alain M. Gardier,Jean-Pierre Changeux +12 more
TL;DR: It is established that α6β2* nAChRs are functional and sensitive to α-conotoxin MII inhibition, and somato-dendritic (nonα6)α4β2- nA ChRs most likely contribute to nicotine reinforcement.
Journal ArticleDOI
Mice Deficient in the α7 Neuronal Nicotinic Acetylcholine Receptor Lack α-Bungarotoxin Binding Sites and Hippocampal Fast Nicotinic Currents
Avi Orr-Urtreger,Finn M. Göldner,Mayuko Saeki,Isabel Lorenzo,Leah Goldberg,Mariella De Biasi,John A. Dani,James W. Patrick,Arthur L. Beaudet +8 more
TL;DR: It is demonstrated that the α7 subunit is not essential for normal development or for apparently normal neurological function, but the mice may prove to have subtle phenotypic abnormalities and will be valuable in defining the functional role of this gene product in vivo.