Alpha-conotoxins as pharmacological probes of nicotinic acetylcholine receptors

Acta Pharmacologica Sinica

Volumn 30, Issue 6, 2009, Pages 771-783

  Azam, Layla ^a   McIntosh, J Michael ^a,b  

^a UNIVERSITY OF UTAH   (United States)

^b UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

Author keywords

AChBP; Alpha conotoxin; Conus; Muscle nicotinic acetylcholine receptor; Neuronal nicotinc acetylcholine receptor; Nicotine; Torpedo

Indexed keywords

ALPHA CONOTOXIN AC1 1A; ALPHA CONOTOXIN AC1 1B; ALPHA CONOTOXIN ANIA; ALPHA CONOTOXIN ANIB; ALPHA CONOTOXIN ANIC; ALPHA CONOTOXIN AUIA; ALPHA CONOTOXIN AUIB; ALPHA CONOTOXIN CNIA; ALPHA CONOTOXIN CNIB; ALPHA CONOTOXIN EI; ALPHA CONOTOXIN EPI; ALPHA CONOTOXIN GI; ALPHA CONOTOXIN GIA; ALPHA CONOTOXIN GIC; ALPHA CONOTOXIN GID; ALPHA CONOTOXIN GII; ALPHA CONOTOXIN IMI; ALPHA CONOTOXIN IMII; ALPHA CONOTOXIN MI; ALPHA CONOTOXIN MII; ALPHA CONOTOXIN OMIA; ALPHA CONOTOXIN PIB; ALPHA CONOTOXIN SI; ALPHA CONOTOXIN SIA; ALPHA CONOTOXIN SII; ALPHA CONOTOXIN SRIA; ALPHA CONOTOXIN SRIB; MARINE TOXIN; NICOTINIC RECEPTOR; UNCLASSIFIED DRUG; UNINDEXED DRUG;

AMINO ACID SEQUENCE; CYCLIZATION; DRUG BIOAVAILABILITY; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG STABILITY; HUMAN; NEUROTRANSMITTER RELEASE; NOCICEPTION; NONHUMAN; PARKINSON DISEASE; REVIEW; STRUCTURE ACTIVITY RELATION;

ANIMALS; CENTRAL NERVOUS SYSTEM; CONOTOXINS; CONUS SNAIL; DRUG DELIVERY SYSTEMS; HUMANS; NEUROMUSCULAR JUNCTION; PAIN; PARKINSON DISEASE; PROTEIN ISOFORMS; RECEPTORS, NICOTINIC;

EID: 67649133580     PISSN: 16714083     EISSN: 17457254     Source Type: Journal    
DOI: 10.1038/aps.2009.47     Document Type: Review

References (135)

1. Gray WR, Olivera BM, Cruz LJ. Peptide toxins from venomous Conus snails. Annu Rev Biochem 1988; 57: 665-700.
2. McIntosh JM, Jones RM. Cone venom - from accidental stings to deliberate injection. Toxicon 2001; 39: 1447-51.
3. Terlau H, Olivera BM. Conus venoms: a rich source of novel ion channel-targeted peptides. Physiol Rev 2004; 84: 41-68.
4. Armishaw CJ, Alewood PF. Conotoxins as research tools and drug leads. Curr Protein Pept Sci 2005; 6: 221-40.
5. Norton RS, Olivera BM. Conotoxins down under. Toxicon 2006; 48: 780-98.
6. Olivera BM, Teichert RW. Diversity of the neurotoxic Conus peptides: a model for concerted pharmacological discovery. Mol Interv 2007; 7: 251-60.
7. McIntosh JM, Olivera BM, Cruz LJ. Conus peptides as probes for ion channels. Methods Enzymol 1999; 294: 605-24.
8. Janes RW. alpha-Conotoxins as selective probes for nicotinic acetylcholine receptor subclasses. Curr Opin Pharmacol 2005; 5: 280-92.
9. Olivera BM, Quik M, Vincler M, McIntosh JM. Subtype-selective conopeptides targeted to nicotinic receptors: concerted discovery and biomedical applications. Channels (Austin) 2008; 2(2): 143-52.
10. Gray WR, Luque A, Olivera BM, Barret J, Cruz LJ. Peptide toxins from Conus geographus venom. J Biol Chem 1981; 256: 4734-40.
11. McManus OB, Musick JR, Gonzalez C. Peptides isolated from the venom of Conus geographus block neuromuscular transmission. Neurosci Let 1981; 25: 57-62.
12. McManus OB, Musick JR. Postsynaptic block of frog neuro-muscular transmission by conotoxin GI. J Neurosci 1985; 5: 110-6.
13. Blount K, Johnson A, Prior C, Marshall IG. alpha-Conotoxin GI produces tetanic fade at the rat neuromuscular junction. Toxicon 1992; 30: 835-42.
14. Marshall IG, Harvey AL. Selective neuromuscular blocking properties of alpha-conotoxins in vivo. Toxicon 1990; 28: 231-4.
15. Luetje CW, Wada K, Rogers S, Abramson SN, Tsuji K, Heinemann S, et al. Neurotoxins distinguish between different neuronal nicotinic acetylcholine receptor subunit combinations. J Neuro chem 1990; 55: 632-40.
16. Johnson DS, Martinez J, Elgoyhen AB, Heinemann SF, McIntosh JM. alpha-Conotoxin ImI exhibits subtype-specific nicotinic acetylcholine receptor blockade: preferential inhibition of homomeric alpha 7 and alpha 9 receptors. Mol Pharmacol 1995; 48: 194-9.
17. McIntosh M, Cruz LJ, Hunkapiller MW, Gray WR, Olivera BM. Isolation and structure of a peptide toxin from the marine snail Conus magus. Arch Biochem Biophys 1982; 218: 329-34.
18. Zafaralla GC, Ramilo C, Gray WR, Karlstrom R, Olivera BM, Cruz LJ. Phylogenetic specificity of cholinergic ligands: alpha-conotoxin SI. Biochemistry 1988; 27: 7102-5.
19. Myers RA, Zafaralla GC, Gray WR, Abbott J, Cruz LJ, Olivera BM. alpha-Conotoxins small peptide probes of nicotinic acetylcholine receptors. Biochemistry 1991; 30: 9370-7.
20. Ramilo CA, Zafaralla GC, Nadasdi L, Hammerland LG, Yoshikami D, Gray WR, et al. Novel alpha- and omega-conotoxins from Conus striatus venom. Biochemistry 1992; 31: 9919-26.
21. Favreau P, Krimm I, Le Gall F, Bobenrieth MJ, Lamthanh H, Bouet F, et al. Biochemical characterization and nuclear magnetic resonance structure of novel alpha-conotoxins isolated from the venom of Conus consors. Biochemistry 1999; 38: 6317-26.
22. Liu L, Chew G, Hawrot E, Chi C, Wang C. Two potent alpha3/5 conotoxins from piscivorous Conus achatinus. Acta Biochim Bio-phys Sin (Shanghai) 2007; 39: 438-44.
23. Kreienkamp HJ, Sine SM, Maeda RK, Taylor P. Glycosylation sites selectively interfere with alpha-toxin binding to the nicotinic acetylcholine receptor. J Biol Chem 1994; 269: 8108-14.
24. Groebe DR, Dumm JM, Levitan ES, Abramson SN. alpha-Cono-toxins selectively inhibit one of the two acetylcholine binding sites of nicotinic receptors. Mol Pharmacol 1995; 48: 105-11.
25. Luo S, McIntosh JM. Iodo-alpha-conotoxin MI selectively binds the alpha/delta subunit interface of muscle nicotinic acetylcholine receptors. Biochemistry 2004; 43: 6656-62.
26. Hann RM, Pagan OR, Eterovic VA. Te alpha-conotoxins GI and MI distinguish between the nicotinic acetylcholine receptor agonist sites while SI does not. Biochemistry 1994; 33: 14058-63.
27. Groebe DR, Gray WR, Abramson SN. Determinants involved in the afnity of alpha-conotoxins GI and SI for the muscle subtype of nicotinic acetylcholine receptors. Biochemistry 1997; 36: 6469-74.
28. Hann RM, Pagan OR, Gregory LM, Jacome T, Eterovic VA. Te 9-arginine residue of alpha-conotoxin GI is responsible for its selective high afnity for the alphagamma agonist site on the electric organ acetylcholine receptor. Biochemistry 1997; 36: 9051-6.
29. Benie AJ, Whitford D, Hargitai B, Barany G, Janes RW. Solution structure of alpha-conotoxin SI. FEBS Let 2000; 476: 287-95.
30. Sine SM, Kreienkamp HJ, Bren N, Maeda R, Taylor P. Molecular dissection of subunit interfaces in the acetylcholine receptor: identifcation of determinants of alpha-conotoxin M1 selectivity. Neuron 1995; 15: 205-11.
31. Bren N, Sine SM. Hydrophobic pairwise interactions stabilize alpha-conotoxin MI in the muscle acetylcholine receptor binding site. J Biol Chem 2000; 275: 12692-700.
32. Jacobsen RB, DelaCruz RG, Grose JH, McIntosh JM, Yoshikami D, Olivera BM. Critical residues infuence the afnity and selectivity of alpha-conotoxin MI for nicotinic acetylcholine receptors. Biochemistry 1999; 38: 13310-5.
33. Kasheverov IE, Zhmak MN, Vulfus CA, Gorbacheva EV, Mord-vintsev DY, Utkin YN, et al. Alpha-conotoxin analogs with additional positive charge show increased selectivity towards Torpedo californica and some neuronal subtypes of nicotinic acetylcholine receptors. FEBS J 2006; 273: 4470-81.
34. Martinez JS, Olivera BM, Gray WR, Craig AG, Groebe DR, Abramson SN, et al. alpha-Conotoxin EI a new nicotinic acetyl-choline receptor antagonist with novel selectivity. Biochemistry 1995; 34: 14519-26.
35. Park KH, Suk JE, Jacobsen R, Gray WR, McIntosh JM, Han KH. Solution conformation of alpha-conotoxin EI a neuromuscular toxin specifc for the alpha 1/delta subunit interface of torpedo nicotinic acetylcholine receptor. J Biol Chem 2001; 276: 49028- 33.
36. Lopez-Vera E, Aguilar MB, Schiavon E, Marinzi C, Ortiz E, Resta-no Cassulini R, et al. Novel alpha-conotoxins from Conus spurius and the alpha-conotoxin EI share high-affinity potentiation and low-afnity inhibition of nicotinic acetylcholine receptors. FEBS J 2007; 274: 3972-85.
37. Lopez-Vera E, Jacobsen RB, Ellison M, Olivera BM, Teichert RW. A novel alpha conotoxin (alpha-PIB) isolated from C, purpura-scens is selective for skeletal muscle nicotinic acetylcholine receptors. Toxicon 2007; 49: 1193-9.
38. McIntosh JM, Yoshikami D, Mahe E, Nielsen DB, Rivier JE, Gray WR, et al. A nicotinic acetylcholine receptor ligand of unique specifcity alpha-conotoxin ImI. J Biol Chem 1994; 269: 16733-9.
39. Tavazoie SF, Tavazoie MF, McIntosh JM, Olivera BM, Yoshikami D. Diferential block of nicotinic synapses on B versus C neurones in sympathetic ganglia of frog by alpha-conotoxins MII and ImI. Br J Pharmacol 1997; 120: 995-1000.
40. Pereira EF, Alkondon M, McIntosh JM, Albuquerque EX. Alpha-conotoxin-ImI: a competitive antagonist at alpha-bungarotoxin-sensitive neuronal nicotinic receptors in hippocampal neurons. J Pharmacol Exp Ter 1996; 278: 1472-83.
41. Quiram PA, Sine SM. Structural elements in alpha-conotoxin ImI essential for binding to neuronal alpha7 receptors. J Biol Chem 1998; 273: 11007-11.
42. Hansen SB, Talley TT, Radic Z, Taylor P. Structural and ligand recognition characteristics of an acetylcholine-binding protein from Aplysia californica. J Biol Chem 2004; 279: 24197-202.
43. Ulens C, Hogg RC, Celie PH, Bertrand D, Tsetlin V, Smit AB, et al. Structural determinants of selective alpha-conotoxin binding to a nicotinic acetylcholine receptor homolog AChBP. Proc Natl Acad Sci USA 2006; 103: 3615-20.
44. Hansen SB, Sulzenbacher G, Huxford T, Marchot P, Taylor P, Bourne Y. Structures of Aplysia AChBP complexes with nicotinic agonists and antagonists reveal distinctive binding interfaces and conformations. EMBO J 2005; 24: 3635-46.
45. Quiram PA Sine SM. Identifcation of residues in the neuronal alpha7 acetylcholine receptor that confer selectivity for conotoxin ImI. J Biol Chem 1998; 273: 11001-6.
46. Quiram PA, Jones JJ, Sine SM. Pairwise interactions between neuronal alpha7 acetylcholine receptors and alpha-conotoxin ImI. J Biol Chem 1999; 274: 19517-24.
47. Armishaw CJ, Daly NL, Nevin ST, Adams DJ, Craik DJ, Alewood PF. Alpha-selenoconotoxins a new class of potent alpha7 neu-ronal nicotinic receptor antagonists. J Biol Chem 2006; 281: 14136-14143.
48. MacRaild CA, Illesinghe J, van Lierop BJ, Townsend AL, Chebib M, Livet BG, et al. Structure and activity of (2,8)-dicarba-(3,12)-cystino alpha-ImI an alpha-conotoxin containing a nonreducible cystine analogue. J Med Chem 2009; 52: 755-62.
49. Ellison M, McIntosh JM, Olivera BM. Alpha-conotoxins ImI and ImII, similar alpha 7 nicotinic receptor antagonists act at diferent sites. J Biol Chem 2003; 278: 757-64.
50. Ellison M, Gao F, Wang HL, Sine SM, McIntosh JM, Olivera BM. Alpha-conotoxins ImI and ImII target distinct regions of the human alpha7 nicotinic acetylcholine receptor and distinguish human nicotinic receptor subtypes. Biochemistry 2004; 43: 16019-26.
51. Cartier GE, Yoshikami D, Gray WR, Luo S, Olivera BM, McIntosh JM. A new alpha-conotoxin which targets alpha3beta2 nicotinic acetylcholine receptors. J Biol Chem 1996; 271: 7522-8.
52. Champtiaux N, Han ZY, Bessis A, Rossi FM, Zoli M, Marubio L, et al. Distribution and pharmacology of alpha 6-containing nicotinic acetylcholine receptors analyzed with mutant mice. J Neurosci 2002; 22: 1208-17.
53. McIntosh JM, Azam L, Staheli S, Dowell C, Lindstrom JM, Kurya-tov A, et al. Analogs of alpha-conotoxin MII are selective for alpha6-containing nicotinic acetylcholine receptors. Mol Pharmacol 2004; 65: 944-52.
54. Kuryatov A, Olale F, Cooper J, Choi C, Lindstrom J. Human alpha6 AChR subtypes: subunit composition assembly and pharmacological responses. Neuropharmacology 2000; 39: 2570-90.
55. Kulak JM, Nguyen TA, Olivera BM, McIntosh JM. Alpha-conotoxin MII blocks nicotine-stimulated dopamine release in rat striatal synaptosomes. J Neurosci 1997; 17: 5263-70.
56. 3H]dopamine release from rat striatal synaptosomes and slices. J Neurochem 1998; 70: 1069-76.
57. Azam L, McIntosh JM. Effect of novel alpha-conotoxins on nicotine-stimulated [3H]dopamine release from rat striatal synap-tosomes. J Pharmacol Exp Ter 2005; 312: 231-7.
58. 3H]dopamine release. Neuropharmacology 2005; 48: 72-9.
59. Dwoskin LP, Wooters TE, Sumithran SP, Siripurapu KB, Joyce BM, Lockman PR, et al. N,N'-Alkane-diyl- bis-3-picoliniums as nicotinic receptor antagonists: inhibition of nicotine-evoked dopamine release and hyperactivity. J Pharmacol Exp Ter 2008; 326: 563-76.
60. Exley R, Clements MA, Hartung H, McIntosh JM, Cragg SJ. Alpha6-containing nicotinic acetylcholine receptors dominate the nicotine control of dopamine neurotransmission in nucleus ac-cumbens. Neuropsychopharmacology 2008; 33: 2158-66.
61. Perez XA, Bordia T, McIntosh JM, Grady SR, Quik M. Long- term nicotine treatment diferentially regulates striatal alpha6al-pha4beta2* and alpha6(nonalpha4)beta2* nAChR expression and function. Mol Pharmacol 2008; 74: 844-53.
62. Salminen O, Murphy KL, McIntosh JM, Drago J, Marks MJ, Collins AC, et al. Subunit composition and pharmacology of two classes of striatal presynaptic nicotinic acetylcholine receptors mediating dopamine release in mice. Mol Pharmacol 2004; 65: 1526-35.
63. Grady SR, Salminen O, Laverty DC, Whiteaker P, McIntosh JM, Collins AC, et al. Te subtypes of nicotinic acetylcholine receptors on dopaminergic terminals of mouse striatum. Biochem Pharmacol 2007; 74: 1235-46.
64. Salminen O, Drapeau JA, McIntosh JM, Collins AC, Marks MJ, Grady SR. Pharmacology of alpha-conotoxin MII-sensitive subtypes of nicotinic acetylcholine receptors isolated by breeding of null mutant mice. Mol Pharmacol 2007; 71: 1563-71.
65. Meyer EL, Yoshikami D, McIntosh JM. The neuronal nicotinic acetylcholine receptors alpha 4* and alpha 6* diferentially modulate dopamine release in mouse striatal slices. J Neurochem 2008; 105: 1761-9.
66. 125I-alpha-conotoxin MII nicotinic receptors afer nigros-triatal damage in monkeys. Neuroscience 2004; 127: 399-408.
67. McCallum SE, Parameswaran N, Bordia T, McIntosh JM, Grady SR, Quik M. Decrease in alpha3*/alpha6* nicotinic receptors but not nicotine-evoked dopamine release in monkey brain afer nigrostriatal damage. Mol Pharmacol 2005; 68: 737-46.
68. Cui C, Booker TK, Allen RS, Grady SR, Whiteaker P, Marks MJ, et al. Te beta3 nicotinic receptor subunit: a component of alpha-conotoxin MII-binding nicotinic acetylcholine receptors that modulate dopamine release and related behaviors. J Neurosci 2003; 23: 11045-53.
69. Goti C, Moreti M, Clementi F, Riganti L, McIntosh JM, Collins AC, et al. Expression of nigrostriatal alpha 6-containing nicotinic acetylcholine receptors is selectively reduced but not eliminated by beta 3 subunit gene deletion. Mol Pharmacol 2005; 67: 2007- 15.
70. Lai A, Parameswaran N, Khwaja M, Whiteaker P, Lindstrom JM, Fan H, et al. Long-term nicotine treatment decreases striatal alpha 6* nicotinic acetylcholine receptor sites and function in mice. Mol Pharmacol 2005; 67: 1639-47.
71. Perry DC, Mao D, Gold AB, McIntosh JM, Pezzullo JC, Kellar KJ. Chronic nicotine diferentially regulates alpha6- and beta3-containing nicotinic cholinergic receptors in rat brain. J Pharmacol Exp Ter 2007; 322: 306-15.
72. Luo S, Kulak JM, Cartier GE, Jacobsen RB, Yoshikami D, Olivera BM, et al. alpha-conotoxin AuIB selectively blocks alpha3 beta4 nicotinic acetylcholine receptors and nicotine-evoked norepi-nephrine release. J Neurosci 1998; 18: 8571-8579.
73. 3H] norepinephrine release from mouse hippocampal synaptosomes. Mol Pharmacol 2006; 70: 967-76.
74. Harvey SC, McIntosh JM, Cartier GE, Maddox FN, Luetje CW. Determinants of specificity for alpha-conotoxin MII on alpha3-beta2 neuronal nicotinic receptors. Mol Pharmacol 1997; 51: 336-42.
75. Dutertre S, Nicke A, Lewis RJ. Beta2 subunit contribution to 4/7 alpha-conotoxin binding to the nicotinic acetylcholine receptor. J Biol Chem 2005; 280: 30460-8.
76. Azam L, Yoshikami D, McIntosh JM. Amino acid residues that confer high selectivity of the alpha6 nicotinic acetylcholine receptor subunit to alpha-conotoxin MII[S4A, E11A, L15A]. J Biol Chem 2008; 283: 11625-32.
77. 125I-alpha-conotoxin MII identifies a novel nicotinic acetylcholine receptor population in mouse brain. Mol Pharmacol 2000; 57: 913-25.
78. Vishwanath VA , McIntosh JM. Synthesis of fuorescent analogs of alpha-conotoxin MII. Bioconjug Chem 2006; 17: 1612-7.
79. 125I-alpha-conotoxin MII binding sites to nigrostriatal damage in monkey. J Neurosci 2001; 21: 5494-500.
80. Kulak JM, McIntosh JM, Quik M. Loss of nicotinic receptors in monkey striatum afer 1-methyl-4-phenyl-1,2,3,6-tetrahydropyri-dine treatment is due to a decline in alpha-conotoxin MII sites. Mol Pharmacol 2002; 61: 230-8.
81. Quik M, Sum JD, Whiteaker P, McCallum SE, Marks MJ, Musa-chio J, et al. Diferential declines in striatal nicotinic receptor subtype function afer nigrostriatal damage in mice. Mol Pharmacol 2003; 63: 1169-79.
82. Quik M, Bordia T, Forno L, McIntosh JM. Loss of alpha-cono-toxinMII- and A85380-sensitive nicotinic receptors in Parkinson's disease striatum. J Neurochem 2004; 88: 668-79.
83. Bordia T, Grady SR, McIntosh JM, Quik M. Nigrostriatal damage preferentially decreases a subpopulation of alpha6beta2* nAChRs in mouse monkey and Parkinson's disease striatum. Mol Pharmacol 2007; 72: 52-61.
84. Clark RJ, Fischer H, Dempster L, Daly NL, Rosengren KJ, Nevin ST, et al. Engineering stable peptide toxins by means of backbone cyclization: stabilization of the alpha-conotoxin MII. Proc Natl Acad Sci USA 2005; 102: 13767-72.
85. Blanchfield JT, Dutton JL, Hogg RC, Gallagher OP, Craik DJ, Jones A, et al. Synthesis structure elucidation in vitro biological activity toxicity and Caco-2 cell permeability of lipophilic analogues of alpha-conotoxin MII. J Med Chem 2003; 46: 1266-72.
86. Blanchfeld JT, Gallagher OP, Cros C, Lewis RJ, Alewood PF, Toth I. Oral absorption and in vivo biodistribution of alpha-conotoxin MII and a lipidic analogue. Biochem Biophys Res Commun 2007; 361: 97-102.
87. Dowell C, Olivera BM, Garret JE, Staheli ST, Watkins M, Kurya-tov A, et al. Alpha-conotoxin PIA is selective for alpha6 subunit-containing nicotinic acetylcholine receptors. J Neurosci 2003; 23: 8445-52.
88. Chi SW, Kim DH, Olivera BM, McIntosh JM, Han KH. Solution conformation of a neuronal nicotinic acetylcholine receptor antagonist alpha-conotoxin OmIA that discriminates alpha3 vs, alpha6 nAChR subtypes. Biochem Biophys Res Commun 2006; 345: 248-54.
89. Talley T, Olivera BM, Han KH, Christensen SB, Dowell C, Tsi-gelny I, et al. Alpha-conotoxin OmIA is a potent ligand for the acetylcholine-binding protein as well as alpha3beta2 and alpha7 nicotinic acetylcholine receptors. J Biol Chem 2006; 281: 24678- 86.
90. McIntosh JM, Dowell C, Watkins M, Garrett JE, Yoshikami D, Olivera BM. Alpha-conotoxin GIC from Conus geographus a novel peptide antagonist of nicotinic acetylcholine receptors. J Biol Chem 2002; 277: 33610-5.
91. Chi SW, Kim DH, Olivera BM, McIntosh JM, Han KH. Solution conformation of alpha-conotoxin GIC a novel potent antagonist of alpha3beta2 nicotinic acetylcholine receptors. Biochem J 2004; 380: 347-52.
92. Nicke A, Loughnan ML, Millard EL, Alewood PF, Adams DJ, Daly NL, et al. Isolation structure and activity of GID a novel alpha 4/7-conotoxin with an extended N-terminal sequence. J Biol Chem 2003; 278: 3137-44.
93. Millard EL, Nevin ST, Loughnan ML, Nicke A, Clark RJ, Alewood PF, et al. Inhibition of neuronal nicotinic acetylcholine receptor subtypes by alpha-conotoxin GID and analogues. J Biol Chem 2009; 284: 4944-51.
94. Loughnan M, Bond T, Atkins A, Cuevas J, Adams DJ, Broxton NM, et al. alpha-conotoxin EpI a novel sulfated peptide from Conus episcopatus that selectively targets neuronal nicotinic acetyl-choline receptors. J Biol Chem 1998; 273: 15667-74.
95. Nicke A, Samochocki M, Loughnan ML, Bansal PS, Maelicke A, Lewis RJ. Alpha-conotoxins EpI and AuIB switch subtype selectivity and activity in native versus recombinant nicotinic acetyl-choline receptors. FEBS Let 2003; 554: 219-23.
96. Loughnan ML, Nicke A, Jones A, Adams DJ, Alewood PF, Lewis RJ. Chemical and functional identifcation and characterization of novel sulfated alpha-conotoxins from the cone snail Conus anemone. J Med Chem 2004; 47: 1234-41.
97. Grady SR, Meinerz NM, Cao J, Reynolds AM, Picciotto MR, Changeux JP, et al. Nicotinic agonists stimulate acetylcholine release from mouse interpeduncular nucleus: a function mediated by a different nAChR than dopamine release from striatum. J Neurochem 2001; 76: 258-68.
98. Fainzilber M, Hasson A, Oren R, Burlingame AL, Gordon D, Spira ME, et al. New mollusc-specific alpha-conotoxins block Aplysia neuronal acetylcholine receptors. Biochemistry 1994; 33: 9523-9.
99. Wolfender JL, Chu F, Ball H, Wolfender F, Fainzilber M, Baldwin MA, et al. Identifcation of tyrosine sulfation in Conus pennaceus conotoxins alpha-PnIA and alpha-PnIB: further investigation of labile sulfo- and phosphopeptides by electrospray matrix-assisted laser desorption/ionization (MALDI) and atmospheric pressure MALDI mass spectrometry. J Mass Spectrom 1999; 34: 447-54.
100. Luo S, Nguyen TA, Cartier GE, Olivera BM, Yoshikami D, McIntosh JM. Single-residue alteration in alpha-conotoxin PnIA switches its nAChR subtype selectivity. Biochemistry 1999; 38: 14542-8.
101. Hogg RC, Miranda LP, Craik DJ, Lewis RJ, Alewood PF, Adams DJ. Single amino acid substitutions in alpha-conotoxin PnIA shif selectivity for subtypes of the mammalian neuronal nicotinic ace-tylcholine receptor. J Biol Chem 1999; 274: 36559-64.
102. Jin AH, Daly NL, Nevin ST, Wang CI, Dutertre S, Lewis RJ, et al. Molecular engineering of conotoxins: the importance of loop size to alpha-conotoxin structure and function. J Med Chem 2008; 51: 5575-84.
103. Everhart D, Reiller E, Mirzoian A, McIntosh JM, Malhotra A, Lu-etje CW. Identifcation of residues that confer alpha-conotoxin- PnIA sensitivity on the alpha 3 subunit of neuronal nicotinic ace-tylcholine receptors. J Pharmacol Exp Ter 2003; 306: 664-70.
104. Celie PH, Kasheverov IE, Mordvintsev DY, Hogg RC, van Nierop P, van Elk R, et al. Crystal structure of nicotinic acetylcholine receptor homolog AChBP in complex with an alpha-conotoxin PnIA variant. Nat Struct Mol Biol 2005; 12: 582-8.
105. Quiram PA, McIntosh JM, Sine SM. Pairwise interactions between neuronal alpha(7) acetylcholine receptors and alpha- conotoxin PnIB. J Biol Chem 2000; 275: 4889-96.
106. Azam L, Dowell C, Watkins M, Stitzel JA, Olivera BM, McIntosh JM. Alpha-conotoxin BuIA, a novel peptide from Conus bullatus distinguishes among neuronal nicotinic acetylcholine receptors. J Biol Chem 2005; 280: 80-7.
107. Shiembob DL, Roberts RL, Luetje CW, McIntosh JM. Determinants of alpha-conotoxin BuIA selectivity on the nicotinic acetyl-choline receptor beta subunit. Biochemistry 2006; 45: 11200-7.
108. Chi SW, Kim DH, Olivera BM, McIntosh JM, Han KH. NMR structure determination of alpha-conotoxin BuIA a novel neu-ronal nicotinic acetylcholine receptor antagonist with an unusual 4/4 disulfide scaffold. Biochem Biophys Res Commun 2006; 349: 1228-34.
109. Jin AH, Brandstaeter H, Nevin ST, Tan CC, Clark RJ, Adams DJ, et al. Structure of alpha-conotoxin BuIA: infuences of disulfde connectivity on structural dynamics. BMC Struct Biol 2007; 7: 28.
110. Elgoyhen AB, Vetter DE, Katz E, Rothlin CV, Heinemann SF, Boulter J. alpha10: a determinant of nicotinic cholinergic receptor function in mammalian vestibular and cochlear mechanosensory hair cells. Proc Natl Acad Sci USA 2001; 98: 3501-6.
111. Baker ER, Zwart R, Sher E, Millar NS. Pharmacological properties of alpha 9 alpha 10 nicotinic acetylcholine receptors revealed by heterologous expression of subunit chimeras. Mol Pharmacol 2004; 65: 453-60.
112. McIntosh JM, Plazas PV, Watkins M, Gomez-Casati ME, Olivera BM, Elgoyhen AB. A novel alpha-conotoxin PeIA cloned from Conus pergrandis discriminates between rat alpha9alpha10 and alpha7 nicotinic cholinergic receptors. J Biol Chem 2005; 280: 30107-12.
113. Ellison M, Haberlandt C, Gomez-Casati ME, Watkins M, Elgoy-hen AB, McIntosh JM, et al. Alpha-RgIA: a novel conotoxin that specifcally and potently blocks the alpha9alpha10 nAChR. Biochemistry 2006; 45: 1511-7.
114. Sandall DW, Satkunanathan N, Keays DA, Polidano MA, Liping X, Pham V, et al. A novel alpha-conotoxin identifed by gene sequencing is active in suppressing the vascular response to selective stimulation of sensory nerves in vivo. Biochemistry 2003; 42: 6904-11.
115. Clark RJ, Fischer H, Nevin ST, Adams DJ, Craik DJ. Te synthesis structural characterization and receptor specifcity of the alpha- conotoxin Vc1.1. J Biol Chem 2006; 281: 23254-63.
116. Vincler M, Witenauer S, Parker R, Ellison M, Olivera BM, McIn-tosh JM. Molecular mechanism for analgesia involving specific antagonism of alpha9alpha10 nicotinic acetylcholine receptors. Proc Natl Acad Sci USA 2006; 103: 17880-4.
117. Nevin ST, Clark RJ, Klimis H, Christie MJ, Craik DJ, Adams DJ. Are alpha9alpha10 nicotinic acetylcholine receptors a pain target for alpha-conotoxins? Mol Pharmacol 2007; 72: 1406-10.
118. Satkunanathan N, Livet B, Gayler K, Sandall D, Down J, Khalil Z. Alpha-conotoxin Vc1.1 alleviates neuropathic pain and accelerates functional recovery of injured neurones. Brain Res 2005; 1059 (2): 149-58.
119. Livet BG, Sandall DW, Keays D, Down J, Gayler KR, Satkunana-than N, et al. Terapeutic applications of conotoxins that target the neuronal nicotinic acetylcholine receptor. Toxicon 2006; 48: 810-29.
120. Callaghan B, Haythornthwaite A, Berecki G, Clark RJ, Craik DJ, Adams DJ. Analgesic alpha-conotoxins Vc1.1 and Rg1A inhibit N-type calcium channels in rat sensory neurons via GABAB receptor activation. J Neurosci 2008; 28: 10943-51.
121. Ellison M, Feng ZP, Park AJ, Zhang X, Olivera BM, McIntosh JM, et al. Alpha-RgIA a novel conotoxin that blocks the alpha9al-pha10 nAChR: structure and identification of key receptor-binding residues. J Mol Biol 2008; 377: 1216-27.
122. Clark RJ, Daly NL, Halai R, Nevin ST, Adams DJ, Craik DJ. Te three-dimensional structure of the analgesic alpha-conotoxin RgIA. FEBS Let 2008; 582: 597-602.
123. Westermann JC, Clark RJ, Craik DJ. Binding mode of alpha- conotoxins to an acetylcholine binding protein determined by saturation transfer diference NMR. Protein Pept Let 2008; 15: 910-4.
124. Dutertre S, Ulens C, Butner R, Fish A, van Elk R, Kendel Y, et al. AChBP-targeted alpha-conotoxin correlates distinct binding orientations with nAChR subtype selectivity. EMBO J 2007; 26: 3858-67.
125. Yuan DD, Han YH, Wang CG, Chi CW. From the identifcation of gene organization of alpha conotoxins to the cloning of novel toxins. Toxicon 2007; 49: 1135-49.
126. Peng C, Han Y, Sanders T, Chew G, Liu J, Hawrot E, et al. alpha4/7-conotoxin Lp1.1 is a novel antagonist of neuronal nico-tinic acetylcholine receptors. Peptides 2008; 29: 1700-7.
127. Luo S, Zhangsun D, Zhang B, Quan Y, Wu Y. Novel alpha- conotoxins identified by gene sequencing from cone snails native to Hainan and their sequence diversity. J Pept Sci 2006; 12: 693-704.
128. Whiteaker P, Christensen S, Yoshikami D, Dowell C, Watkins M, Gulyas J, et al. Discovery synthesis and structure activity of a highly selective alpha7 nicotinic acetylcholine receptor antagonist. Biochemistry 2007; 46: 6628-38.
129. Innocent N, Livingstone PD, Hone A, Kimura A, Young T, Whiteaker P, et al. Alpha-conotoxin Arenatus IB[V11L, V16D] [corrected] is a potent and selective antagonist at rat and human native alpha7 nicotinic acetylcholine receptors. J Pharmacol Exp Ter 2008; 327: 529-37.
130. 125I-alpha- cono-toxin ArIB[V11L; V16A] a selective alpha7 nicotinic acetylcho-line receptor antagonist. J Pharmacol Exp Ter 2008; 325: 910-9.
131. Olivera BM. Conus peptides: biodiversity-based discovery and exogenomics. J Biol Chem 2006; 281: 31173-7.
132. Kuzmin A, Jerlhag E, Liljequist S, Engel J. Efects of subunit selective nACh receptors on operant ethanol self-administration and relapse-like ethanol-drinking behavior. Psychopharmacology (Berl) 2009; 203: 99-108.
133. Jerlhag E, Egecioglu E, Dickson SL, Svensson L, Engel JA. Alpha- conotoxin MII-sensitive nicotinic acetylcholine receptors are involved in mediating the ghrelin-induced locomotor stimulation and dopamine overflow in nucleus accumbens. Eur Neuropsy-chopharmacol 2008; 18: 508-18.
134. Jerlhag E, Grotli M, Luthman K, Svensson L, Engel JA. Role of the subunit composition of central nicotinic acetylcholine receptors for the stimulatory and dopamine-enhancing efects of etha-nol. Alcohol Alcohol 2006; 41: 486-93.
135. Larsson A, Jerlhag E, Svensson L, Soderpalm B, Engel JA. Is an alpha-conotoxin MII-sensitive mechanism involved in the neuro-chemical stimulatory and rewarding efects of ethanol? Alcohol 2004; 34: 239-50. 136 Maslennikov IV, Shenkarev ZO, Zhmak MN, Ivanov V T, Methfes-sel C, Tsetlin VI, et al. NMR spatial structure of alpha-conotoxin ImI reveals a common scafold in snail and snake toxins recognizing neuronal nicotinic acetylcholine receptors. FEBS Let 1999; 444: 275-80. 137 Chi SW, Lee SH, Kim DH, Kim JS, Olivera BM, McIntosh JM, et al. Solution structure of alpha-conotoxin PIA a novel antagonist of alpha6 subunit containing nicotinic acetylcholine receptors. Biochem Biophys Res Commun 2005; 338: 1990-7.