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Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition.

Publication ,  Journal Article
Chuang, HH; Prescott, ED; Kong, H; Shields, S; Jordt, SE; Basbaum, AI; Chao, MV; Julius, D
Published in: Nature
June 21, 2001

Tissue injury generates endogenous factors that heighten our sense of pain by increasing the response of sensory nerve endings to noxious stimuli. Bradykinin and nerve growth factor (NGF) are two such pro-algesic agents that activate G-protein-coupled (BK2) and tyrosine kinase (TrkA) receptors, respectively, to stimulate phospholipase C (PLC) signalling pathways in primary afferent neurons. How these actions produce sensitization to physical or chemical stimuli has not been elucidated at the molecular level. Here, we show that bradykinin- or NGF-mediated potentiation of thermal sensitivity in vivo requires expression of VR1, a heat-activated ion channel on sensory neurons. Diminution of plasma membrane phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) levels through antibody sequestration or PLC-mediated hydrolysis mimics the potentiating effects of bradykinin or NGF at the cellular level. Moreover, recruitment of PLC-gamma to TrkA is essential for NGF-mediated potentiation of channel activity, and biochemical studies suggest that VR1 associates with this complex. These studies delineate a biochemical mechanism through which bradykinin and NGF produce hypersensitivity and might explain how the activation of PLC signalling systems regulates other members of the TRP channel family.

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Published In

Nature

DOI

ISSN

0028-0836

Publication Date

June 21, 2001

Volume

411

Issue

6840

Start / End Page

957 / 962

Location

England

Related Subject Headings

  • Xenopus laevis
  • Type C Phospholipases
  • Signal Transduction
  • Receptors, Drug
  • Receptor, trkA
  • Protein Kinase C
  • Phosphatidylinositol 4,5-Diphosphate
  • Pain
  • Oocytes
  • Nociceptors
 

Citation

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Chuang, H. H., Prescott, E. D., Kong, H., Shields, S., Jordt, S. E., Basbaum, A. I., … Julius, D. (2001). Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition. Nature, 411(6840), 957–962. https://doi.org/10.1038/35082088
Chuang, H. H., E. D. Prescott, H. Kong, S. Shields, S. E. Jordt, A. I. Basbaum, M. V. Chao, and D. Julius. “Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition.Nature 411, no. 6840 (June 21, 2001): 957–62. https://doi.org/10.1038/35082088.
Chuang HH, Prescott ED, Kong H, Shields S, Jordt SE, Basbaum AI, et al. Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition. Nature. 2001 Jun 21;411(6840):957–62.
Chuang, H. H., et al. “Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition.Nature, vol. 411, no. 6840, June 2001, pp. 957–62. Pubmed, doi:10.1038/35082088.
Chuang HH, Prescott ED, Kong H, Shields S, Jordt SE, Basbaum AI, Chao MV, Julius D. Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition. Nature. 2001 Jun 21;411(6840):957–962.
Journal cover image

Published In

Nature

DOI

ISSN

0028-0836

Publication Date

June 21, 2001

Volume

411

Issue

6840

Start / End Page

957 / 962

Location

England

Related Subject Headings

  • Xenopus laevis
  • Type C Phospholipases
  • Signal Transduction
  • Receptors, Drug
  • Receptor, trkA
  • Protein Kinase C
  • Phosphatidylinositol 4,5-Diphosphate
  • Pain
  • Oocytes
  • Nociceptors