Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Luo S, Kulak JM, Cartier GE, Jacobsen RB, Yoshikami D, Olivera BM, McIntosh JM.
???displayArticle.abstract???
Neuronal nicotinic acetylcholine receptors (nAChRs) with putative alpha3 beta4-subunits have been implicated in the mediation of signaling in various systems, including ganglionic transmission peripherally and nicotine-evoked neurotransmitter release centrally. However, progress in the characterization of these receptors has been hampered by a lack of alpha3 beta4-selective ligands. In this report, we describe the purification and characterization of an alpha3 beta4 nAChR antagonist, alpha-conotoxin AuIB, from the venom of the "court cone," Conus aulicus. We also describe the total chemical synthesis of this and two related peptides that were also isolated from the venom. alpha-Conotoxin AuIB blocks alpha3 beta4 nAChRs expressed in Xenopus oocytes with an IC50 of 0.75 microM, a kon of 1.4 x 10(6) min-1 M-1, a koff of 0.48 min-1, and a Kd of 0.5 microM. Furthermore, alpha-conotoxin AuIB blocks the alpha3 beta4 receptor with >100-fold higher potency than other receptor subunit combinations, including alpha2 beta2, alpha2 beta4, alpha3 beta2, alpha4 beta2, alpha4 beta4, and alpha1 beta1 gamma delta. Thus, AuIB is a novel, selective probe for alpha3 beta4 nAChRs. AuIB (1-5 microM) blocks 20-35% of the nicotine-stimulated norepinephrine release from rat hippocampal synaptosomes, whereas nicotine-evoked dopamine release from striatal synaptosomes is not affected. Conversely, the alpha3 beta2-specific alpha-conotoxin MII (100 nM) blocks 33% of striatal dopamine release but not hippocampal norepinephrine release. This suggests that in the respective systems, alpha3 beta4-containing nAChRs mediate norepinephrine release, whereas alpha3 beta2-containing receptors mediate dopamine release.
Cartier,
A new alpha-conotoxin which targets alpha3beta2 nicotinic acetylcholine receptors.
1996, Pubmed,
Xenbase
Cartier,
A new alpha-conotoxin which targets alpha3beta2 nicotinic acetylcholine receptors.
1996,
Pubmed
,
Xenbase Clarke,
Release of [3H]-noradrenaline from rat hippocampal synaptosomes by nicotine: mediation by different nicotinic receptor subtypes from striatal [3H]-dopamine release.
1996,
Pubmed Conroy,
Neurons can maintain multiple classes of nicotinic acetylcholine receptors distinguished by different subunit compositions.
1995,
Pubmed Flores,
Neuronal nicotinic receptor expression in sensory neurons of the rat trigeminal ganglion: demonstration of alpha3beta4, a novel subtype in the mammalian nervous system.
1996,
Pubmed Gerzanich,
Homomers of alpha 8 and alpha 7 subunits of nicotinic receptors exhibit similar channel but contrasting binding site properties.
1994,
Pubmed
,
Xenbase Johnson,
alpha-Conotoxin ImI exhibits subtype-specific nicotinic acetylcholine receptor blockade: preferential inhibition of homomeric alpha 7 and alpha 9 receptors.
1995,
Pubmed
,
Xenbase Kaiser,
Differential inhibition by alpha-conotoxin-MII of the nicotinic stimulation of [3H]dopamine release from rat striatal synaptosomes and slices.
1998,
Pubmed
,
Xenbase Kulak,
Alpha-conotoxin MII blocks nicotine-stimulated dopamine release in rat striatal synaptosomes.
1997,
Pubmed Lewis,
The ion channel properties of a rat recombinant neuronal nicotinic receptor are dependent on the host cell type.
1997,
Pubmed
,
Xenbase Martinez,
alpha-Conotoxin EI, a new nicotinic acetylcholine receptor antagonist with novel selectivity.
1995,
Pubmed McIntosh,
A nicotinic acetylcholine receptor ligand of unique specificity, alpha-conotoxin ImI.
1994,
Pubmed McIntosh,
Isolation and structure of a peptide toxin from the marine snail Conus magus.
1982,
Pubmed Mongeau,
The serotonergic and noradrenergic systems of the hippocampus: their interactions and the effects of antidepressant treatments.
1997,
Pubmed Papke,
Inhibition of nicotinic acetylcholine receptors by bis (2,2,6,6-tetramethyl- 4-piperidinyl) sebacate (Tinuvin 770), an additive to medical plastics.
1994,
Pubmed
,
Xenbase Penn,
Competition in retinogeniculate patterning driven by spontaneous activity.
1998,
Pubmed Pereira,
Alpha-conotoxin-ImI: a competitive antagonist at alpha-bungarotoxin-sensitive neuronal nicotinic receptors in hippocampal neurons.
1996,
Pubmed Pontieri,
Effects of nicotine on the nucleus accumbens and similarity to those of addictive drugs.
1996,
Pubmed Rapier,
Stereoselective nicotine-induced release of dopamine from striatal synaptosomes: concentration dependence and repetitive stimulation.
1988,
Pubmed Sacaan,
Pharmacological characterization of neuronal acetylcholine gated ion channel receptor-mediated hippocampal norepinephrine and striatal dopamine release from rat brain slices.
1995,
Pubmed Sargent,
The diversity of neuronal nicotinic acetylcholine receptors.
1993,
Pubmed Sershen,
Characterization of nicotinic receptors involved in the release of noradrenaline from the hippocampus.
1997,
Pubmed Sine,
Molecular dissection of subunit interfaces in the acetylcholine receptor: identification of determinants of alpha-conotoxin M1 selectivity.
1995,
Pubmed Sivilotti,
Recombinant nicotinic receptors, expressed in Xenopus oocytes, do not resemble native rat sympathetic ganglion receptors in single-channel behaviour.
1997,
Pubmed
,
Xenbase Tavazoie,
Differential block of nicotinic synapses on B versus C neurones in sympathetic ganglia of frog by alpha-conotoxins MII and ImI.
1997,
Pubmed Ullian,
Rapid synaptic transmission in the avian ciliary ganglion is mediated by two distinct classes of nicotinic receptors.
1997,
Pubmed Wonnacott,
Presynaptic nicotinic ACh receptors.
1997,
Pubmed Zoli,
Identification of four classes of brain nicotinic receptors using beta2 mutant mice.
1998,
Pubmed
