Journal article
Bradykinin-induced nuclear factor of activated T-cells-dependent transcription in rat dorsal root ganglion neurons
Molecular pharmacology, v 72(2), pp 303-310
01 Aug 2007
PMID: 17485565
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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 B-2 receptors evoked concentration-dependent (EC50 = 6.0 +/- 0.3 nM) increases in intracellular Ca2+ concentration ([Ca2+](i)) in a proportion of dorsal root ganglion neurons in primary culture. These [Ca2+] 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 2-min exposure to bradykinin induced the translocation of GFP-NFAT4 from the cytoplasm to the nucleus. Translocation was partially inhibited by the 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 B-2 receptor, PLC activation, and inositol triphosphate-mediated Ca2+ release. Transcription was not inhibited by capsazepine. Finally, as indicated by quantitative reverse transcription-polymerase chain reaction, bradykinin elicited an increase in cyclooxygenase mRNA. This increase was sensitive to calcineurin and B-2 receptor inhibition. These findings suggest a mechanism by which short-lived bradykinin-mediated stimuli can enact lasting changes in nociceptor function and sensitivity.
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Details
- Title
- Bradykinin-induced nuclear factor of activated T-cells-dependent transcription in rat dorsal root ganglion neurons
- Creators
- Joshua G. Jackson - University of Minnesota Medical CenterYuriy M. Usachev - University of Minnesota Medical CenterStanley A. Thayer - University of Minnesota Medical Center
- Publication Details
- Molecular pharmacology, v 72(2), pp 303-310
- Publisher
- Amer Soc Pharmacology Experimental Therapeutics
- Number of pages
- 8
- Grant note
- R37DA007304 / NATIONAL INSTITUTE ON DRUG ABUSE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); European Commission R01 DA007304; DA07097; DA07304; DA11806; R37 DA007304 / NIDA NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000248282900010
- Scopus ID
- 2-s2.0-34547193818
- Other Identifier
- 991021900192804721
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- Web of Science research areas
- Pharmacology & Pharmacy