Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • 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
  • 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
Journal of Pharmacology and Experimental Therapeutics
  • 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
Journal of Pharmacology and Experimental Therapeutics

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • 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
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleTOXICOLOGY

Pb2+ via Protein Kinase C Inhibits Nicotinic Cholinergic Modulation of Synaptic Transmission in the Hippocampus

Maria F. M. Braga, Edna F. R. Pereira, Arpad Mike and Edson X. Albuquerque
Journal of Pharmacology and Experimental Therapeutics November 2004, 311 (2) 700-710; DOI: https://doi.org/10.1124/jpet.104.070466
Maria F. M. Braga
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Edna F. R. Pereira
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Arpad Mike
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Edson X. Albuquerque
  • 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
Loading

Abstract

The present study was designed to investigate the effects of Pb2+ on modulation of synaptic transmission by nicotinic receptors (nAChRs) in the rat hippocampus. To this end, inhibitory and excitatory postsynaptic currents (IPSCs and EPSCs, respectively) were recorded by means of the whole-cell mode of the patch-clamp technique from rat hippocampal neurons in culture. Acetylcholine (ACh, 1 mM; 1-s pulses) triggered GABA release via activation of α4β2* and α7* nAChRs. It also triggered glutamate release via activation of α7* nAChRs. Pb2+ (0.1 and 1 μM) blocked ACh-triggered transmitter release. Blockade by Pb2+ of ACh-triggered IPSCs was partially reversible upon washing of the neurons. In contrast, even after 30- to 60-min washing, there was no reversibility of Pb2+-induced blockade of ACh-triggered EPSCs. The effects of Pb2+ on GABA release triggered by activation of α7* and α4β2* nACRs were mimicked by the protein kinase C (PKC) activator phorbol-12-myristate-13-acetate (1 μM) and blocked by the indolocarbazole Gö 7874 (50 nM) and the bisindolylmaleimide Ro-31-8425 (150 nM), which are selective PKC inhibitors. After washing of fully functional neuronal networks that had been exposed for 5 min to Pb2+, the irreversible inhibition by Pb2+ of ACh-triggered glutamate release was partially overridden by a disinhibitory mechanism that is likely to involve α4β2* nAChR activation in interneurons that synapse onto other interneurons synapsing onto pyramidal neurons. Long-lasting inhibition of α7* nAChR modulation of synaptic transmission may contribute to the persistent cognitive impairment that results from childhood Pb2+ intoxication.

Footnotes

  • ↵1 Current address: Department of Psychiatry, F. Edward Herbert School of Medicine, Uniformed Services University of Health Sciences, Rockville, MD 20842.

  • ↵2 Current address: Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.

  • This work was supported by U.S. Public Health Service Grants ES05730 and NS41671 (for E.X.A.). Part of this work was presented as an abstract at the 1999 Meeting of the Society for Neurosciences.

  • According to the current status of the nomenclature for nicotinic receptors (nAChRs) and their subunits (Lukas et al., 1999), the asterisk next to nAChR subunits throughout the text is meant to indicate that the exact receptor subunit composition is not known.

  • doi:10.1124/jpet.104.070466.

  • ABBREVIATIONS: VGCC, voltage-gated Ca2+ channels; NMDA, N-methyl-d-aspartate; nAChR, nicotinic acetylcholine receptor; PKC, protein kinase C; IPSC, inhibitory postsynaptic current; EPSC, excitatory postsynaptic current; ACh, acetylcholine; PMA, phorbol 12-myristate 13-acetate; CNQX, 6-cyano-7-nitroquinoxaline-2,3-dione; AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; MLA, methyllycaconitine; DHβE, dihydro-β-erythroidine.

    • Received April 30, 2004.
    • Accepted June 28, 2004.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET 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

Journal of Pharmacology and Experimental Therapeutics: 311 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 311, Issue 2
1 Nov 2004
  • Table of Contents
  • About the Cover
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Journal of Pharmacology and Experimental Therapeutics 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.
Pb2+ via Protein Kinase C Inhibits Nicotinic Cholinergic Modulation of Synaptic Transmission in the Hippocampus
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleTOXICOLOGY

Pb2+ via Protein Kinase C Inhibits Nicotinic Cholinergic Modulation of Synaptic Transmission in the Hippocampus

Maria F. M. Braga, Edna F. R. Pereira, Arpad Mike and Edson X. Albuquerque
Journal of Pharmacology and Experimental Therapeutics November 1, 2004, 311 (2) 700-710; DOI: https://doi.org/10.1124/jpet.104.070466

Citation Manager Formats

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

Pb2+ via Protein Kinase C Inhibits Nicotinic Cholinergic Modulation of Synaptic Transmission in the Hippocampus

Maria F. M. Braga, Edna F. R. Pereira, Arpad Mike and Edson X. Albuquerque
Journal of Pharmacology and Experimental Therapeutics November 1, 2004, 311 (2) 700-710; DOI: https://doi.org/10.1124/jpet.104.070466
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Tolerability profile of a GalNAc3-conjugated ASO in Monkeys
  • Preclinical Safety of Lung Instillation of Thyroid Hormone
  • Nefazodone Inhibits Anaerobic Glycolysis
Show more Toxicology

Similar Articles

  • 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 JPET
  • 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
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2021 by the American Society for Pharmacology and Experimental Therapeutics