ß-adrenergic receptor agonists delay while antagonists accelerate epithelial wound healing: Evidence of an endogenous adrenergic network within the corneal epithelium
Article first published online: 16 JAN 2007
Copyright © 2007 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 211, Issue 1, pages 261–272, April 2007
How to Cite
Pullar, C. E., Zhao, M., Song, B., Pu, J., Reid, B., Ghoghawala, S., McCaig, C. and Isseroff, R. R. (2007), ß-adrenergic receptor agonists delay while antagonists accelerate epithelial wound healing: Evidence of an endogenous adrenergic network within the corneal epithelium. J. Cell. Physiol., 211: 261–272. doi: 10.1002/jcp.20934
- Issue published online: 29 JAN 2007
- Article first published online: 16 JAN 2007
- Manuscript Accepted: 6 OCT 2006
- Manuscript Received: 18 AUG 2006
- NIH. Grant Numbers: AR 48827, AR 44518
- The Royal Society of Edinburgh International Exchange Program Grant (CEP and MZ), University of Aberdeen Visiting Scholars Fellowship (CEP)
Wound healing is a complex and well-orchestrated biological process. Corneal epithelial cells (CECs) must respond quickly to trauma to rapidly restore barrier function and protect the eye from noxious agents. They express a high level of ß2-adrenergic receptors but their function is unknown. Here, we report the novel finding that they form part of a regulatory network in the corneal epithelium, capable of modulating corneal epithelial wound repair. ß-adrenergic receptor agonists delay CEC migration via a protein phosphatase 2A-mediated mechanism and decrease both electric field-directed migration and corneal wound healing. Conversely, ß-adrenergic receptor antagonists accelerate CEC migration, enhance electric field-mediated directional migration, and promote corneal wound repair. We demonstrate that CECs express key enzymes required for epinephrine (ß-adrenergic receptor agonist) synthesis in the cytoplasm and can detect epinephrine in cell extracts. We propose that the mechanism for the pro-motogenic effect of the ß-adrenergic antagonist is blockade of the ß2-adrenergic receptor preventing autocrine catecholamine binding. Further investigation of this network will improve our understanding of one of the most frequently prescribed class of drugs. J. Cell. Physiol. 211: 261–272, 2007. © 2007 Wiley-Liss, Inc.