 |
 Previous Article | Next Article 
The Journal of Neuroscience, November 1, 1998, 18(21):8571-8579
 -Conotoxin AuIB Selectively Blocks 3 4
Nicotinic Acetylcholine Receptors and Nicotine-Evoked Norepinephrine
Release
Siqin
Luo1,
Jennifer M.
Kulak1,
G. Edward
Cartier1,
Richard B.
Jacobsen1,
Doju
Yoshikami1,
Baldomero M.
Olivera1, and
J. Michael
McIntosh1, 2
Departments of 1 Biology and 2 Psychiatry,
University of Utah, Salt Lake City, Utah 84112
Neuronal nicotinic acetylcholine receptors (nAChRs) with putative
 3 4-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 34-selective ligands. In this report, we describe the
purification and characterization of an 34 nAChR antagonist, -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. -Conotoxin AuIB blocks 34 nAChRs
expressed in Xenopus oocytes with an IC50 of
0.75 µM, a kon of 1.4 × 106 min-1
M 1, a koff
of 0.48 min-1, and a
Kd of 0.5 µM. Furthermore,
-conotoxin AuIB blocks the 34 receptor with
>100-fold higher potency than other receptor subunit combinations,
including 22, 24, 32, 42, 44, and
11  . Thus, AuIB is a novel, selective probe for
34 nAChRs. AuIB (1-5 µM) 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
32-specific -conotoxin MII (100 nM)
blocks 33% of striatal dopamine release but not hippocampal
norepinephrine release. This suggests that in the respective systems,
34-containing nAChRs mediate norepinephrine release, whereas
32-containing receptors mediate dopamine release.
Key words:
nicotinic acetylcholine receptor; conotoxin; 34; norepinephrine; dopamine; hippocampus; striatum; synaptosomes; Xenopus oocytes
Copyright © 1998 Society for Neuroscience 0270-6474/98/18218571-09$05.00/0
This article has been cited by other articles:
|
|
|
|
 
C. Armishaw, A. A. Jensen, T. Balle, R. J. Clark, K. Harpsoe, C. Skonberg, T. Liljefors, and K. Stromgaard
Rational Design of {alpha}-Conotoxin Analogues Targeting {alpha}7 Nicotinic Acetylcholine Receptors: IMPROVED ANTAGONISTIC ACTIVITY BY INCORPORATION OF PROLINE DERIVATIVES
J. Biol. Chem.,
April 3, 2009;
284(14):
9498 - 9512.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. B. Sargent
Nicotinic Receptors Concentrated in the Subsynaptic Membrane Do Not Contribute Significantly to Synaptic Currents at an Embryonic Synapse in the Chicken Ciliary Ganglion
J. Neurosci.,
March 25, 2009;
29(12):
3749 - 3759.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. W. Kamendi, Q. Cheng, O. Dergacheva, C. Gorini, H. S. Jameson, X. Wang, J. M. McIntosh, and D. Mendelowitz
Abolishment of Serotonergic Neurotransmission to Cardiac Vagal Neurons During and After Hypoxia and Hypercapnia With Prenatal Nicotine Exposure
J Neurophysiol,
March 1, 2009;
101(3):
1141 - 1150.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. I. Westphalen, R. S. Gomez, and H. C. Hemmings Jr
Nicotinic receptor-evoked hippocampal norepinephrine release is highly sensitive to inhibition by isoflurane
Br. J. Anaesth.,
March 1, 2009;
102(3):
355 - 360.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. R. Grady, M. Moretti, M. Zoli, M. J. Marks, A. Zanardi, L. Pucci, F. Clementi, and C. Gotti
Rodent Habenulo-Interpeduncular Pathway Expresses a Large Variety of Uncommon nAChR Subtypes, But Only the {alpha}3{beta}4 and {alpha}3{beta}3{beta}4 Subtypes Mediate Acetylcholine Release
J. Neurosci.,
February 18, 2009;
29(7):
2272 - 2282.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Zwart, A. L. Carbone, M. Moroni, I. Bermudez, A. J. Mogg, E. A. Folly, L. M. Broad, A. C. Williams, D. Zhang, C. Ding, et al.
Sazetidine-A Is a Potent and Selective Agonist at Native and Recombinant {alpha}4{beta}2 Nicotinic Acetylcholine Receptors
Mol. Pharmacol.,
June 1, 2008;
73(6):
1838 - 1843.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Lendvai and E. S. Vizi
Nonsynaptic Chemical Transmission Through Nicotinic Acetylcholine Receptors
Physiol Rev,
April 1, 2008;
88(2):
333 - 349.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Azam and J. M. McIntosh
Characterization of Nicotinic Acetylcholine Receptors That Modulate Nicotine-Evoked [3H]Norepinephrine Release from Mouse Hippocampal Synaptosomes
Mol. Pharmacol.,
September 1, 2006;
70(3):
967 - 976.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. T. Talley, B. M. Olivera, K.-H. Han, S. B. Christensen, C. Dowell, I. Tsigelny, K.-Y. Ho, P. Taylor, and J. M. McIntosh
{alpha}-Conotoxin OmIA Is a Potent Ligand for the Acetylcholine-binding Protein as Well as {alpha}3beta2 and {alpha}7 Nicotinic Acetylcholine Receptors
J. Biol. Chem.,
August 25, 2006;
281(34):
24678 - 24686.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Schwarz, S. C. Schwarz, O. Dorigo, A. Stutzer, F. Wegner, C. Labarca, P. Deshpande, J. S. Gil, A. J. Berk, and H. A. Lester
Enhanced expression of hypersensitive {alpha}4* nAChR in adult mice increases the loss of midbrain dopaminergic neurons
FASEB J,
May 1, 2006;
20(7):
935 - 946.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Barik and S. Wonnacott
Indirect Modulation by {alpha}7 Nicotinic Acetylcholine Receptors of Noradrenaline Release in Rat Hippocampal Slices: Interaction with Glutamate and GABA Systems and Effect of Nicotine Withdrawal
Mol. Pharmacol.,
February 1, 2006;
69(2):
618 - 628.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. Zhu, R. R. Stewart, J. M. McIntosh, and F. F. Weight
Activation of Nicotinic Acetylcholine Receptors Increases the Frequency of Spontaneous GABAergic IPSCs in Rat Basolateral Amygdala Neurons
J Neurophysiol,
November 1, 2005;
94(5):
3081 - 3091.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-Z. Guo, Y. Liu, E. M. Sorenson, and V. A. Chiappinelli
Synaptically Released and Exogenous ACh Activates Different Nicotinic Receptors to Enhance Evoked Glutamatergic Transmission in the Lateral Geniculate Nucleus
J Neurophysiol,
October 1, 2005;
94(4):
2549 - 2560.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. L. Obaid, M. E. Nelson, J. Lindstrom, and B. M. Salzberg
Optical studies of nicotinic acetylcholine receptor subtypes in the guinea-pig enteric nervous system
J. Exp. Biol.,
August 1, 2005;
208(15):
2981 - 3001.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-J. Cao, C. S. Surowy, and P. S. Puttfarcken
Nicotinic Acetylcholine Receptor-Mediated [3H]Dopamine Release from Hippocampus
J. Pharmacol. Exp. Ther.,
March 1, 2005;
312(3):
1298 - 1304.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. I. Chernyavsky, J. Arredondo, L. M. Marubio, and S. A. Grando
Differential regulation of keratinocyte chemokinesis and chemotaxis through distinct nicotinic receptor subtypes
J. Cell Sci.,
November 1, 2004;
117(23):
5665 - 5679.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Orb, J. Wieacker, C. Labarca, C. Fonck, H. A. Lester, and J. Schwarz
Knockin mice with Leu9'Ser {alpha}4-nicotinic receptors: substantia nigra dopaminergic neurons are hypersensitive to agonist and lost postnatally
Physiol Genomics,
August 11, 2004;
18(3):
299 - 307.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Salminen, K. L. Murphy, J. M. McIntosh, J. Drago, M. J. Marks, A. C. Collins, and S. R. Grady
Subunit Composition and Pharmacology of Two Classes of Striatal Presynaptic Nicotinic Acetylcholine Receptors Mediating Dopamine Release in Mice
Mol. Pharmacol.,
June 1, 2004;
65(6):
1526 - 1535.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. McIntosh, L. Azam, S. Staheli, C. Dowell, J. M. Lindstrom, A. Kuryatov, J. E. Garrett, M. J. Marks, and P. Whiteaker
Analogs of {alpha}-Conotoxin MII Are Selective for {alpha}6-Containing Nicotinic Acetylcholine Receptors
Mol. Pharmacol.,
April 1, 2004;
65(4):
944 - 952.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
H. TERLAU and B. M. OLIVERA
Conus Venoms: A Rich Source of Novel Ion Channel-Targeted Peptides
Physiol Rev,
January 1, 2004;
84(1):
41 - 68.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Dowell, B. M. Olivera, J. E. Garrett, S. T. Staheli, M. Watkins, A. Kuryatov, D. Yoshikami, J. M. Lindstrom, and J. M. McIntosh
{alpha}-Conotoxin PIA Is Selective for {alpha}6 Subunit-Containing Nicotinic Acetylcholine Receptors
J. Neurosci.,
September 17, 2003;
23(24):
8445 - 8452.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q. Nai, J. M. McIntosh, and J. F. Margiotta
Relating Neuronal Nicotinic Acetylcholine Receptor Subtypes Defined by Subunit Composition and Channel Function
Mol. Pharmacol.,
February 1, 2003;
63(2):
311 - 324.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Nicke, M. L. Loughnan, E. L. Millard, P. F. Alewood, D. J. Adams, N. L. Daly, D. J. Craik, and R. J. Lewis
Isolation, Structure, and Activity of GID, a Novel alpha 4/7-Conotoxin with an Extended N-terminal Sequence
J. Biol. Chem.,
January 24, 2003;
278(5):
3137 - 3144.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Dutton, P. S. Bansal, R. C. Hogg, D. J. Adams, P. F. Alewood, and D. J. Craik
A New Level of Conotoxin Diversity, a Non-native Disulfide Bond Connectivity in alpha -Conotoxin AuIB Reduces Structural Definition but Increases Biological Activity
J. Biol. Chem.,
December 6, 2002;
277(50):
48849 - 48857.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. McIntosh, C. Dowell, M. Watkins, J. E. Garrett, D. Yoshikami, and B. M. Olivera
alpha -Conotoxin GIC from Conus geographus, a Novel Peptide Antagonist of Nicotinic Acetylcholine Receptors
J. Biol. Chem.,
September 6, 2002;
277(37):
33610 - 33615.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. K. Miller, S. P. Sumithran, and L. P. Dwoskin
Bupropion Inhibits Nicotine-Evoked [3H]Overflow from Rat Striatal Slices Preloaded with [3H]Dopamine and from Rat Hippocampal Slices Preloaded with [3H]Norepinephrine
J. Pharmacol. Exp. Ther.,
September 1, 2002;
302(3):
1113 - 1122.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Quik, Y. Polonskaya, J. M. Kulak, and J. M. McIntosh
Vulnerability of 125I-{alpha}-Conotoxin MII Binding Sites to Nigrostriatal Damage in Monkey
J. Neurosci.,
August 1, 2001;
21(15):
5494 - 5500.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Barazangi and L. W. Role
Nicotine-Induced Enhancement of Glutamatergic and GABAergic Synaptic Transmission in the Mouse Amygdala
J Neurophysiol,
July 1, 2001;
86(1):
463 - 474.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M.-L. Si and T. J. F. Lee
Presynaptic alpha 7-Nicotinic Acetylcholine Receptors Mediate Nicotine-Induced Nitric Oxidergic Neurogenic Vasodilation in Porcine Basilar Arteries
J. Pharmacol. Exp. Ther.,
July 1, 2001;
298(1):
122 - 128.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
J. H Hicks, J. A Dani, and R. A J Lester
Regulation of the sensitivity of acetylcholine receptors to nicotine in rat habenula neurons
J. Physiol.,
December 15, 2000;
529(3):
579 - 597.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Bansal, J. H. Singer, B. J. Hwang, W. Xu, A. Beaudet, and M. B. Feller
Mice Lacking Specific Nicotinic Acetylcholine Receptor Subunits Exhibit Dramatically Altered Spontaneous Activity Patterns and Reveal a Limited Role for Retinal Waves in Forming ON and OFF Circuits in the Inner Retina
J. Neurosci.,
October 15, 2000;
20(20):
7672 - 7681.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. W. Oppenheim, D. Prevette, A. D'Costa, S. Wang, L. J. Houenou, and J. M. McIntosh
Reduction of Neuromuscular Activity Is Required for the Rescue of Motoneurons from Naturally Occurring Cell Death by Nicotinic-Blocking Agents
J. Neurosci.,
August 15, 2000;
20(16):
6117 - 6124.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Bibevski, Y. Zhou, J. M. McIntosh, R. E. Zigmond, and M. E. Dunlap
Functional Nicotinic Acetylcholine Receptors That Mediate Ganglionic Transmission in Cardiac Parasympathetic Neurons
J. Neurosci.,
July 1, 2000;
20(13):
5076 - 5082.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. M. Francis, R. W. Vazquez, R. L. Papke, and R. E. Oswald
Subtype-Selective Inhibition of Neuronal Nicotinic Acetylcholine Receptors by Cocaine Is Determined by the alpha 4 and beta 4 Subunits
Mol. Pharmacol.,
July 1, 2000;
58(1):
109 - 119.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
S. Dhar, F. Nagy, J. M. McIntosh, and H. N. Sapru
Receptor subtypes mediating depressor responses to microinjections of nicotine into medial NTS of the rat
Am J Physiol Regulatory Integrative Comp Physiol,
July 1, 2000;
279(1):
R132 - R140.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-H. Cho, K. H. Mok, B. M. Olivera, J. M. McIntosh, K.-H. Park, and K.-H. Han
Nuclear Magnetic Resonance Solution Conformation of alpha -Conotoxin AuIB, an alpha 3beta 4 Subtype-selective Neuronal Nicotinic Acetylcholine Receptor Antagonist
J. Biol. Chem.,
March 17, 2000;
275(12):
8680 - 8685.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Lena, A. de Kerchove d'Exaerde, M. Cordero-Erausquin, N. Le Novere, M. del Mar Arroyo-Jimenez, and J.-P. Changeux
Diversity and distribution of nicotinic acetylcholine receptors in the locus ceruleus neurons
PNAS,
October 12, 1999;
96(21):
12126 - 12131.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Cardoso, S. J. Brozowski, L. E. Chavez-Noriega, M. Harpold, C. F. Valenzuela, and R. A. Harris
Effects of Ethanol on Recombinant Human Neuronal Nicotinic Acetylcholine Receptors Expressed in Xenopus Oocytes
J. Pharmacol. Exp. Ther.,
May 1, 1999;
289(2):
774 - 780.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
D Kristufek, E Stocker, S Boehm, and S Huck
Somatic and prejunctional nicotinic receptors in cultured rat sympathetic neurones show different agonist profiles
J. Physiol.,
May 1, 1999;
516(3):
739 - 756.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Giniatullin, S. Di Angelantonio, C. Marchetti, E. Sokolova, L. Khiroug, and A. Nistri
Calcitonin Gene-Related Peptide Rapidly Downregulates Nicotinic Receptor Function and Slowly Raises Intracellular Ca2+ in Rat Chromaffin Cells In Vitro
J. Neurosci.,
April 15, 1999;
19(8):
2945 - 2953.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. McIntosh, G. O. Corpuz, R. T. Layer, J. E. Garrett, J. D. Wagstaff, G. Bulaj, A. Vyazovkina, D. Yoshikami, L. J. Cruz, and B. M. Olivera
Isolation and Characterization of a Novel Conus Peptide with Apparent Antinociceptive Activity
J. Biol. Chem.,
October 13, 2000;
275(42):
32391 - 32397.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z.-P. Feng, J. Hamid, C. Doering, G. M. Bosey, T. P. Snutch, and G. W. Zamponi
Residue Gly1326 of the N-type Calcium Channel alpha 1B Subunit Controls Reversibility of omega -Conotoxin GVIA and MVIIA Block
J. Biol. Chem.,
May 4, 2001;
276(19):
15728 - 15735.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K.-H. Park, J.-E. Suk, R. Jacobsen, W. R. Gray, J. M. McIntosh, and K.-H. Han
Solution Conformation of alpha -Conotoxin EI, a Neuromuscular Toxin Specific for the alpha 1/delta Subunit Interface of Torpedo Nicotinic Acetylcholine Receptor
J. Biol. Chem.,
December 21, 2001;
276(52):
49028 - 49033.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
