April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
CB1 Activation Reduces TRPV1-induced Responses in Human Corneal Epithelial Cells
Author Affiliations & Notes
  • Hua Yang
    Biological Sciences, SUNY College of Optometry, New York, New York
  • Stefan Mergler
    Department of Ophthalmology, University Medicine Charite Berlin, Berlin, Germany
  • Zheng Wang
    Biological Sciences, SUNY College of Optometry, New York, New York
  • Kulandaiappan Varadaraj
    Physiology & Biophysics, SUNY, Stony Brook, Stony Brook, New York
  • Sindhu S. Kumari
    Physiology & Biophysics, SUNY, Stony Brook, Stony Brook, New York
  • Peter S. Reinach
    Biological Sciences, SUNY College of Optometry, New York, New York
  • Footnotes
    Commercial Relationships  Hua Yang, None; Stefan Mergler, None; Zheng Wang, None; Kulandaiappan Varadaraj, None; Sindhu S. Kumari, None; Peter S. Reinach, None
  • Footnotes
    Support  EY04795, EY20506 and W81XWH-09-2-0162
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 2053. doi:
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      Hua Yang, Stefan Mergler, Zheng Wang, Kulandaiappan Varadaraj, Sindhu S. Kumari, Peter S. Reinach; CB1 Activation Reduces TRPV1-induced Responses in Human Corneal Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2053.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : In primary sensory neurons, cannabinoid 1 (CB1) receptors suppress transient receptor potential vanilloid type 1 (TRPV1) channel activation. As TRPV1 is expressed in the mouse corneal epithelium and human corneal epithelial cells (HCEC), we determined in both tissue types if protein-protein interaction is associated with CB1 suppression of TRPV1 function.

Methods: : Immunostaining and Western blot analysis probed for CB1 and TRPV1 colocalization and interaction. The CB1 agonist/antagonist pair: WIN55, 212-2 (WIN) and AM251 (AM) was used along with the mixed endogenous TRPV1/CB1 agonist, anandamide (AEA). The TRPV1 agonist/antagonist pair: capsaicin (CAP) and capsazepine (CPZ) was also used. ELISA determined proinflammatory cytokine release. TRPV1 channel activity was characterized with the planar-patch clamp technique.

Results: : In the mouse corneal epithelium, CB1 and TRPV1 colocalization was identified. Furthermore, coimmunoprecipitation analysis of HCEC identified protein-protein interaction between CB1 and TRPV1. CAP (10 µM)-induced 2.1, 2.5, 1.8-fold increases in IL-6, IL-8 and TNF-α release, respectively, Joint CB1/TRPV1 activation with 10 µM AEA induced rises that were 30-50% smaller than those obtained by CAP alone. However, these rises induced by AEA were restored to CAP obtained levels by initially blocking AEA activation of CB1 with AM251. CAP in HCEC induced 2.1-fold increases in cation channel current at a holding potential of 0 mV. This response to CAP could be suppressed during exposure to WIN.

Conclusions: : Protein-protein interaction between CB1 and TRPV1 is consistent with our findings that CB1 activation can dampen both CAP-induced increases in current, proinflammatory cytokine and chemoattractant release. These effects indicate that changes in CB1 activity modulate TRPV1 activation. Taken together, CB1 may be a potential drug target to reduce corneal epithelial inflammation resulting from injury-induced TRPV1 activation by release of endogenous metabolites.

Keywords: cornea: epithelium • signal transduction • inflammation 
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