QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, September 17, 2003, 23(24):8445-8452

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (58) Citing Articles via Google Scholar Google Scholar Articles by Dowell, C. Articles by McIntosh, J. M. Search for Related Content PubMed PubMed Citation Articles by Dowell, C. Articles by McIntosh, J. M.

 Previous Article  |  Next Article 

-Conotoxin PIA Is Selective for 6 Subunit-Containing Nicotinic Acetylcholine Receptors

Cheryl Dowell,¹ Baldomero M. Olivera,¹ James E. Garrett,⁴ Sarah T. Staheli,¹ Maren Watkins,² Alexander Kuryatov,⁵ Doju Yoshikami,¹ Jon M. Lindstrom,⁵ and J. Michael McIntosh^1,3

Departments of ¹Biology, ²Pathology, and ³Psychiatry, University of Utah, Salt Lake City, Utah 84112, ⁴Cognetix, Salt Lake City, Utah 84108, and ⁵Department of Neuroscience, University of Pennsylvania Medical School, Philadelphia, Pennsylvania 19104

Until now, there have been no antagonists to discriminate between heteromeric nicotinic acetylcholine receptors (nAChRs) containing the very closely related 6 and 3 subunits. nAChRs containing 3, 4, or 6 subunits in combination with 2, occasionally 4, and sometimes 3 or 5 subunits, are thought to play important roles in cognitive function, pain perception, and the reinforcing properties of nicotine. We cloned a novel gene from the predatory marine snail Conus purpurascens. The predicted peptide, -conotoxin PIA, potently blocks the chimeric 6/323 subunit combination as expressed in oocytes but neither the muscle nor the major neuronal nAChR 42. Additionally, this toxin is the first described ligand to discriminate between nAChRs containing 6 and 3 subunits. Exploiting the unusual intron conservation of conotoxin genes may represent a more general approach for defining conotoxin ligand scaffolds to discriminate among closely related receptor populations.

Key words: nicotinic; -conotoxin; 6; 2; 3; Conus

---

Received May 5, 2003; revised July 22, 2003; accepted July 24, 2003.

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]

				L. Azam, D. Yoshikami, and J. M. McIntosh Amino Acid Residues That Confer High Selectivity of the {alpha}6 Nicotinic Acetylcholine Receptor Subunit to {alpha}-Conotoxin MII[S4A,E11A,L15A] J. Biol. Chem., April 25, 2008; 283(17): 11625 - 11632. [Abstract] [Full Text] [PDF]

				E. JERLHAG, M. GROTLI, K. LUTHMAN, L. SVENSSON, and J. A. ENGEL ROLE OF THE SUBUNIT COMPOSITION OF CENTRAL NICOTINIC ACETYLCHOLINE RECEPTORS FOR THE STIMULATORY AND DOPAMINE-ENHANCING EFFECTS OF ETHANOL Alcohol Alcohol., September 1, 2006; 41(5): 486 - 493. [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]

				M. Quik and J. M. McIntosh Striatal {alpha}6* Nicotinic Acetylcholine Receptors: Potential Targets for Parkinson's Disease Therapy J. Pharmacol. Exp. Ther., February 1, 2006; 316(2): 481 - 489. [Abstract] [Full Text] [PDF]

				T. Endo, Y. Yanagawa, K. Obata, and T. Isa Nicotinic Acetylcholine Receptor Subtypes Involved in Facilitation of GABAergic Inhibition in Mouse Superficial Superior Colliculus J Neurophysiol, December 1, 2005; 94(6): 3893 - 3902. [Abstract] [Full Text] [PDF]

				S. Dutertre, A. Nicke, and R. J. Lewis {beta}2 Subunit Contribution to 4/7 {alpha}-Conotoxin Binding to the Nicotinic Acetylcholine Receptor J. Biol. Chem., August 26, 2005; 280(34): 30460 - 30468. [Abstract] [Full Text] [PDF]

				R. L. Papke, J. D. Buhr, M. M. Francis, K. I. Choi, J. S. Thinschmidt, and N. A. Horenstein The Effects of Subunit Composition on the Inhibition of Nicotinic Receptors by the Amphipathic Blocker 2,2,6,6-Tetramethylpiperidin-4-yl Heptanoate Mol. Pharmacol., June 1, 2005; 67(6): 1977 - 1990. [Abstract] [Full Text] [PDF]

				L. Azam, C. Dowell, M. Watkins, J. A. Stitzel, B. M. Olivera, and J. M. McIntosh {alpha}-Conotoxin BuIA, a Novel Peptide from Conus bullatus, Distinguishes among Neuronal Nicotinic Acetylcholine Receptors J. Biol. Chem., January 7, 2005; 280(1): 80 - 87. [Abstract] [Full Text] [PDF]

				L. Azam and J. M. McIntosh Effect of Novel {alpha}-Conotoxins on Nicotine-Stimulated [3H]Dopamine Release from Rat Striatal Synaptosomes J. Pharmacol. Exp. Ther., January 1, 2005; 312(1): 231 - 237. [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]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help