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ß‐adrenergic receptor agonists delay while antagonists accelerate epithelial wound healing: Evidence of an endogenous adrenergic network within the corneal epithelium
Author(s) -
Pullar Christine E.,
Zhao Min,
Song Bing,
Pu Jin,
Reid Brian,
Ghoghawala Shahed,
McCaig Colin,
Isseroff R. Rivkah
Publication year - 2007
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20934
Subject(s) - corneal epithelium , wound healing , receptor , microbiology and biotechnology , agonist , epithelium , adrenergic , epinephrine , adrenergic receptor , pharmacology , biology , cornea , neuroscience , medicine , endocrinology , immunology , genetics
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.