MolPharm

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

Molecular Pharmacology Fast Forward
First published on May 7, 2007; DOI: 10.1124/mol.107.035048

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
mol.107.035048v1
72/2/303    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jackson, J. G
Right arrow Articles by Thayer, S. A
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jackson, J. G
Right arrow Articles by Thayer, S. A


Received for publication February 9, 2007.
Revised April 24, 2007.
Accepted for publication May 7, 2007.

Bradykinin-Induced NFAT-Dependent Transcription in Rat Dorsal Root Ganglion Neurons

Joshua G Jackson 1, Yuriy M Usachev 2, Stanley A Thayer 3*

1 Univ of Minnesota 2 Univ of Iowa 3 University of Minnesota

* Address correspondence to: E-mail: sathayer{at}umn.edu

Abstract

Bradykinin produced at sites of tissue injury and inflammation elicits acute pain and alters the sensitivity of nociceptive neurons to subsequent stimuli. We tested the hypothesis that bradykinin could elicit long lasting changes in nociceptor function by activating members of the Nuclear Factor of Activated T-cells (NFAT) family of transcription factors. Bradykinin activation of B2 receptors evoked concentration dependent (EC50 = 6.0 ± 0.3 nM) increases in intracellular Ca2+ concentration ([Ca2+]i) in a proportion of dorsal root ganglion (DRG) neurons in primary culture. These [Ca2+]i increases were sensitive to inhibition of phospholipase C (PLC) and depletion of Ca2+ stores. In neurons expressing a green fluorescent protein (GFP)-NFAT4 fusion protein, a two minute exposure to bradykinin induced the translocation of GFP-NFAT4 from the cytoplasm to the nucleus. Translocation was partially inhibited by removal of extracellular Ca2+ and was blocked by inhibition of calcineurin. Furthermore, bradykinin triggered a concentration-dependent increase in NFAT-mediated transcription of a luciferase gene reporter (EC50 = 24.2 ± 0.1 nM). This depended on the B2 receptor, PLC activation and IP3 mediated Ca2+ release. Transcription was not inhibited by capsazepine. Lastly, as indicated by quantitative RT-PCR, bradykinin elicited an increase in cyclooxygenase (cox-2) mRNA. This increase was sensitive to calcineurin and B2 receptor inhibition. These findings suggest a mechanism by which short-lived bradykinin-mediated stimuli can enact lasting changes in nociceptor function and sensitivity.


Key words: Neuropeptides, Bradykinin, Phospholipase C's, NFAT, Ca imaging, Regulation of gene expression


This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
M. Nieves-Cintron, G. C. Amberg, M. F. Navedo, J. D. Molkentin, and L. F. Santana
The control of Ca2+ influx and NFATc3 signaling in arterial smooth muscle during hypertension
PNAS, October 7, 2008; 105(40): 15623 - 15628.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] --
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2007 by the American Society for Pharmacology and Experimental Therapeutics