HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 1, 80-87, January 7, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/1/80    most recent M406281200v1 Submit a Letter to Editor 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 PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Azam, L. Articles by McIntosh, J. M. Search for Related Content PubMed PubMed Citation Articles by Azam, L. Articles by McIntosh, J. M. Social Bookmarking                      What's this?

-Conotoxin BuIA, a Novel Peptide from Conus bullatus, Distinguishes among Neuronal Nicotinic Acetylcholine Receptors^*

Layla Azam, Cheryl Dowell, Maren Watkins, Jerry A. Stitzel¶, Baldomero M. Olivera, and J. Michael McIntosh||**

From the Departments of Biology, Pathology, and ^||Psychiatry, University of Utah, Salt Lake City, Utah 84112 and the ^¶Department of Integrative Physiology and Institute for Behavioral Genetics, University of Colorado, Boulder, Colorado 80309

Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels. Subunits, together with 2 and/or 4 subunits, form ligand-binding sites at / subunit interfaces. Predatory marine snails of the genus Conus are a rich source of nAChR-targeted peptides. Using conserved features of the -conotoxin signal sequence and 3'-untranslated sequence region, we have cloned a novel gene from the fish-eating snail, Conus bullatus; the gene codes for a previously unreported -conotoxin with unusual 4/4 spacing of amino acids in the two disulfide loops. Chemical synthesis of the predicted mature toxin was performed. The resulting peptide, -conotoxin BuIA, was tested on cloned nAChRs expressed in Xenopus oocytes. The peptide potently blocks numerous rat nAChR subtypes, with highest potency for 3- and chimeric 6-containing nAChRs; BuIA blocks 6/32 nAChRs with a 40,000-fold lower IC₅₀ than 42 nAChRs. The kinetics of toxin unblock are dependent on the subunit. nAChRs with a 4 subunit have very slow off-times, compared with the corresponding 2 subunit-containing nAChR. In each instance, rat x4 may be distinguished from rat x2 by the large difference in time to recover from toxin block. Similar results are obtained when comparing mouse 32 to mouse 34, and human 32 to human 34, indicating that the subunit dependence extends across species. Thus, -conotoxin BuIA also represents a novel probe for distinguishing between 2- and 4-containing nAChRs.

Received for publication, June 7, 2004 , and in revised form, October 25, 2004.

^* This work was supported by Kirschstein-NRSA Postdoctoral Fellowship DA 016835 (to L. A.), and National Institutes of Health Grants MH 53631 (to J. M. M.), DA 14369 (to J. A. S.), and GM 48677 (to B. M. O.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^** To whom correspondence should be addressed: Dept. of Biology, University of Utah, 257 South 1400 East, Salt Lake City, Utah 84112. Tel.: 801-585-3622; Fax: 801-585-5010; E-mail: mcintosh{at}biology.utah.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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]

				M. Vincler, S. Wittenauer, R. Parker, M. Ellison, B. M. Olivera, and J. M. McIntosh Molecular mechanism for analgesia involving specific antagonism of {alpha}9{alpha}10 nicotinic acetylcholine receptors PNAS, November 21, 2006; 103(47): 17880 - 17884. [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]

				K. B. Mihalak, F. I. Carroll, and C. W. Luetje Varenicline Is a Partial Agonist at {alpha}4beta2 and a Full Agonist at {alpha}7 Neuronal Nicotinic Receptors Mol. Pharmacol., September 1, 2006; 70(3): 801 - 805. [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. M. McIntosh, P. V. Plazas, M. Watkins, M. E. Gomez-Casati, B. M. Olivera, and A. B. Elgoyhen A Novel {alpha}-Conotoxin, PeIA, Cloned from Conus pergrandis, Discriminates between Rat {alpha}9{alpha}10 and {alpha}7 Nicotinic Cholinergic Receptors J. Biol. Chem., August 26, 2005; 280(34): 30107 - 30112. [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]