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Research ArticleCellular and Molecular

Activation of Estrogen Receptor α Enhances Bradykinin Signaling in Peripheral Sensory Neurons of Female Rats

Matthew P. Rowan, Kelly A. Berg, James L. Roberts, Kenneth M. Hargreaves and William P. Clarke
Journal of Pharmacology and Experimental Therapeutics June 2014, 349 (3) 526-532; DOI: https://doi.org/10.1124/jpet.114.212977
Matthew P. Rowan
Department of Pharmacology (M.P.R., K.A.B., J.L.R., K.M.H., W.P.C.) and Endodontics (K.M.H.), University of Texas Health Science Center at San Antonio, San Antonio, Texas
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Kelly A. Berg
Department of Pharmacology (M.P.R., K.A.B., J.L.R., K.M.H., W.P.C.) and Endodontics (K.M.H.), University of Texas Health Science Center at San Antonio, San Antonio, Texas
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James L. Roberts
Department of Pharmacology (M.P.R., K.A.B., J.L.R., K.M.H., W.P.C.) and Endodontics (K.M.H.), University of Texas Health Science Center at San Antonio, San Antonio, Texas
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Kenneth M. Hargreaves
Department of Pharmacology (M.P.R., K.A.B., J.L.R., K.M.H., W.P.C.) and Endodontics (K.M.H.), University of Texas Health Science Center at San Antonio, San Antonio, Texas
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William P. Clarke
Department of Pharmacology (M.P.R., K.A.B., J.L.R., K.M.H., W.P.C.) and Endodontics (K.M.H.), University of Texas Health Science Center at San Antonio, San Antonio, Texas
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Abstract

Numerous studies have demonstrated that females have a higher risk of experiencing several pain disorders with either greater frequency or severity than males. Although the mechanisms that underlie this sex disparity remain unclear, several studies have shown an important role for sex steroids, such as estrogen, in the modulation of nociception. Receptors for estrogen are present in primary afferent neurons in the trigeminal and dorsal root ganglia, and brief exposure to estrogen increases responses to the inflammatory mediator bradykinin (BK). However, the mechanism for estrogen-mediated enhancement of BK signaling is not fully understood. The aim of the present study was to evaluate the relative contributions of estrogen receptor α (ERα), ERβ, and G protein–coupled estrogen receptor 1 (GPER) to the enhanced signaling of the inflammatory mediator BK by 17β-estradiol (17β-E2) in primary sensory neurons from female rats in culture (ex vivo) and in behavioral assays of nociception in vivo. The effects of 17β-E2 on BK responses were mimicked by ERα-selective agonists and blocked by ERα-selective antagonists and by small interfering RNA knockdown of ERα. The data indicate that ERα is required for 17β-E2–mediated enhancement of BK signaling in peripheral sensory neurons in female rats.

Footnotes

    • Received January 9, 2014.
    • Accepted March 5, 2014.
  • This work was supported by the National Institutes of Health National Institute of Neurological Disorders and Stroke [Grants R01-NS055835, R01-NS061884, and R01-NS058655]; the Texas Advanced Research Program [Grant 003659-0023; the Oral and Maxillofacial Surgery Foundation; and the National Institutes of Health National Institute of Dental and Craniofacial Research [Training Grant T32-DE14318] (to M.P.R.).

  • dx.doi.org/10.1124/jpet.114.212977.

  • Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 349 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 349, Issue 3
1 Jun 2014
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Research ArticleCellular and Molecular

ERα Rapidly Enhances Bradykinin Signaling

Matthew P. Rowan, Kelly A. Berg, James L. Roberts, Kenneth M. Hargreaves and William P. Clarke
Journal of Pharmacology and Experimental Therapeutics June 1, 2014, 349 (3) 526-532; DOI: https://doi.org/10.1124/jpet.114.212977

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Research ArticleCellular and Molecular

ERα Rapidly Enhances Bradykinin Signaling

Matthew P. Rowan, Kelly A. Berg, James L. Roberts, Kenneth M. Hargreaves and William P. Clarke
Journal of Pharmacology and Experimental Therapeutics June 1, 2014, 349 (3) 526-532; DOI: https://doi.org/10.1124/jpet.114.212977
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