Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Molecular Pharmacology
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Molecular Pharmacology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

α-Conotoxins Identify the α3β4* Subtype as the Predominant Nicotinic Acetylcholine Receptor Expressed in Human Adrenal Chromaffin Cells

Arik J. Hone, J. Michael McIntosh, Layla Azam, Jon Lindstrom, Linda Lucero, Paul Whiteaker, Juan Passas, Jesús Blázquez and Almudena Albillos
Molecular Pharmacology November 2015, 88 (5) 881-893; DOI: https://doi.org/10.1124/mol.115.100982
Arik J. Hone
Departamento de Farmacología y Terapéutica, Universidad Autónoma de Madrid, Madrid, Spain (A.J.H., A.A.); Departments of Biology and Psychiatry, University of Utah, Salt Lake City, Utah (J.M.M., L.A.); George E. Whalen Veterans Affairs Medical Center, Salt Lake City, Utah (J.M.M.); Department of Neuroscience, University of Pennsylvania Medical School, Philadelphia, Pennsylvania (J.L.); Division of Neurobiology, Barrow Neurological Institute, Phoenix, Arizona (L.L., P.W.); Hospital Doce de Octubre, Madrid, Spain (J.P.); and Hospital Clínico San Carlos Madrid, Spain (J.B.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J. Michael McIntosh
Departamento de Farmacología y Terapéutica, Universidad Autónoma de Madrid, Madrid, Spain (A.J.H., A.A.); Departments of Biology and Psychiatry, University of Utah, Salt Lake City, Utah (J.M.M., L.A.); George E. Whalen Veterans Affairs Medical Center, Salt Lake City, Utah (J.M.M.); Department of Neuroscience, University of Pennsylvania Medical School, Philadelphia, Pennsylvania (J.L.); Division of Neurobiology, Barrow Neurological Institute, Phoenix, Arizona (L.L., P.W.); Hospital Doce de Octubre, Madrid, Spain (J.P.); and Hospital Clínico San Carlos Madrid, Spain (J.B.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Layla Azam
Departamento de Farmacología y Terapéutica, Universidad Autónoma de Madrid, Madrid, Spain (A.J.H., A.A.); Departments of Biology and Psychiatry, University of Utah, Salt Lake City, Utah (J.M.M., L.A.); George E. Whalen Veterans Affairs Medical Center, Salt Lake City, Utah (J.M.M.); Department of Neuroscience, University of Pennsylvania Medical School, Philadelphia, Pennsylvania (J.L.); Division of Neurobiology, Barrow Neurological Institute, Phoenix, Arizona (L.L., P.W.); Hospital Doce de Octubre, Madrid, Spain (J.P.); and Hospital Clínico San Carlos Madrid, Spain (J.B.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jon Lindstrom
Departamento de Farmacología y Terapéutica, Universidad Autónoma de Madrid, Madrid, Spain (A.J.H., A.A.); Departments of Biology and Psychiatry, University of Utah, Salt Lake City, Utah (J.M.M., L.A.); George E. Whalen Veterans Affairs Medical Center, Salt Lake City, Utah (J.M.M.); Department of Neuroscience, University of Pennsylvania Medical School, Philadelphia, Pennsylvania (J.L.); Division of Neurobiology, Barrow Neurological Institute, Phoenix, Arizona (L.L., P.W.); Hospital Doce de Octubre, Madrid, Spain (J.P.); and Hospital Clínico San Carlos Madrid, Spain (J.B.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Linda Lucero
Departamento de Farmacología y Terapéutica, Universidad Autónoma de Madrid, Madrid, Spain (A.J.H., A.A.); Departments of Biology and Psychiatry, University of Utah, Salt Lake City, Utah (J.M.M., L.A.); George E. Whalen Veterans Affairs Medical Center, Salt Lake City, Utah (J.M.M.); Department of Neuroscience, University of Pennsylvania Medical School, Philadelphia, Pennsylvania (J.L.); Division of Neurobiology, Barrow Neurological Institute, Phoenix, Arizona (L.L., P.W.); Hospital Doce de Octubre, Madrid, Spain (J.P.); and Hospital Clínico San Carlos Madrid, Spain (J.B.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Paul Whiteaker
Departamento de Farmacología y Terapéutica, Universidad Autónoma de Madrid, Madrid, Spain (A.J.H., A.A.); Departments of Biology and Psychiatry, University of Utah, Salt Lake City, Utah (J.M.M., L.A.); George E. Whalen Veterans Affairs Medical Center, Salt Lake City, Utah (J.M.M.); Department of Neuroscience, University of Pennsylvania Medical School, Philadelphia, Pennsylvania (J.L.); Division of Neurobiology, Barrow Neurological Institute, Phoenix, Arizona (L.L., P.W.); Hospital Doce de Octubre, Madrid, Spain (J.P.); and Hospital Clínico San Carlos Madrid, Spain (J.B.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Juan Passas
Departamento de Farmacología y Terapéutica, Universidad Autónoma de Madrid, Madrid, Spain (A.J.H., A.A.); Departments of Biology and Psychiatry, University of Utah, Salt Lake City, Utah (J.M.M., L.A.); George E. Whalen Veterans Affairs Medical Center, Salt Lake City, Utah (J.M.M.); Department of Neuroscience, University of Pennsylvania Medical School, Philadelphia, Pennsylvania (J.L.); Division of Neurobiology, Barrow Neurological Institute, Phoenix, Arizona (L.L., P.W.); Hospital Doce de Octubre, Madrid, Spain (J.P.); and Hospital Clínico San Carlos Madrid, Spain (J.B.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jesús Blázquez
Departamento de Farmacología y Terapéutica, Universidad Autónoma de Madrid, Madrid, Spain (A.J.H., A.A.); Departments of Biology and Psychiatry, University of Utah, Salt Lake City, Utah (J.M.M., L.A.); George E. Whalen Veterans Affairs Medical Center, Salt Lake City, Utah (J.M.M.); Department of Neuroscience, University of Pennsylvania Medical School, Philadelphia, Pennsylvania (J.L.); Division of Neurobiology, Barrow Neurological Institute, Phoenix, Arizona (L.L., P.W.); Hospital Doce de Octubre, Madrid, Spain (J.P.); and Hospital Clínico San Carlos Madrid, Spain (J.B.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Almudena Albillos
Departamento de Farmacología y Terapéutica, Universidad Autónoma de Madrid, Madrid, Spain (A.J.H., A.A.); Departments of Biology and Psychiatry, University of Utah, Salt Lake City, Utah (J.M.M., L.A.); George E. Whalen Veterans Affairs Medical Center, Salt Lake City, Utah (J.M.M.); Department of Neuroscience, University of Pennsylvania Medical School, Philadelphia, Pennsylvania (J.L.); Division of Neurobiology, Barrow Neurological Institute, Phoenix, Arizona (L.L., P.W.); Hospital Doce de Octubre, Madrid, Spain (J.P.); and Hospital Clínico San Carlos Madrid, Spain (J.B.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF
Loading

This article has a correction. Please see:

  • Correction to “α-Conotoxins Identify the α3β4* Subtype as the Predominant Nicotinic Acetylcholine Receptor Expressed in Human Adrenal Chromaffin Cells” - February 01, 2016

Abstract

Ligands that selectively inhibit human α3β2 and α6β2 nicotinic acetylcholine receptor (nAChRs) and not the closely related α3β4 and α6β4 subtypes are lacking. Current α-conotoxins (α-Ctxs) that discriminate among these nAChR subtypes in rat fail to discriminate among the human receptor homologs. In this study, we describe the development of α-Ctx LvIA(N9R,V10A) that is 3000-fold more potent on oocyte-expressed human α3β2 than α3β4 and 165-fold more potent on human α6/α3β2β3 than α6/α3β4 nAChRs. This analog was used in conjuction with three other α-Ctx analogs and patch-clamp electrophysiology to characterize the nAChR subtypes expressed by human adrenal chromaffin cells. LvIA(N9R,V10A) showed little effect on the acetylcholine-evoked currents in these cells at concentrations expected to inhibit nAChRs with β2 ligand-binding sites. In contrast, the β4-selective α-Ctx BuIA(T5A,P6O) inhibited >98% of the acetylcholine-evoked current, indicating that most of the heteromeric receptors contained β4 ligand-binding sites. Additional studies using the α6-selective α-Ctx PeIA(A7V,S9H,V10A,N11R,E14A) indicated that the predominant heteromeric nAChR expressed by human adrenal chromaffin cells is the α3β4* subtype (asterisk indicates the possible presence of additional subunits). This conclusion was supported by polymerase chain reaction experiments of human adrenal medulla gland and of cultured human adrenal chromaffin cells that demonstrated prominent expression of RNAs for α3, α5, α7, β2, and β4 subunits and a low abundance of RNAs for α2, α4, α6, and α10 subunits.

Footnotes

    • Received July 22, 2015.
    • Accepted August 31, 2015.
  • A.J.H. holds a Marie Curie International Fellowship from the European Commission [NRHACC-329966]. This work was also supported by Spanish Ministerio de Ciencia y Tecnología [Grant BFU2012-30997 to A.A.]; National Institutes of Health [Grants GM-103801 and GM-48677 to J.M.M., Grant DA030929 to J.L., and Grants R21 DA026627, R21 DA027070S, and R01 DA012242 to P.W.]; and Barrow Neurological Foundation [to P.W.].

  • dx.doi.org/10.1124/mol.115.100982.

  • Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics
View Full Text

MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Molecular Pharmacology: 88 (5)
Molecular Pharmacology
Vol. 88, Issue 5
1 Nov 2015
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
α-Conotoxins Identify the α3β4* Subtype as the Predominant Nicotinic Acetylcholine Receptor Expressed in Human Adrenal Chromaffin Cells
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

α-Conotoxins Identify α3β4 nAChRs in Chromaffin Cells

Arik J. Hone, J. Michael McIntosh, Layla Azam, Jon Lindstrom, Linda Lucero, Paul Whiteaker, Juan Passas, Jesús Blázquez and Almudena Albillos
Molecular Pharmacology November 1, 2015, 88 (5) 881-893; DOI: https://doi.org/10.1124/mol.115.100982

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

α-Conotoxins Identify α3β4 nAChRs in Chromaffin Cells

Arik J. Hone, J. Michael McIntosh, Layla Azam, Jon Lindstrom, Linda Lucero, Paul Whiteaker, Juan Passas, Jesús Blázquez and Almudena Albillos
Molecular Pharmacology November 1, 2015, 88 (5) 881-893; DOI: https://doi.org/10.1124/mol.115.100982
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Action of Org 34167 on HCN channels
  • The effects of echinocystic acid on Kv7 channels
  • Cysteine151 in Keap1 Drives CDDO-Me Pharmacodynamic Action
Show more Articles

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Molecular Pharmacology
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics