β-adrenergic receptor agonists delay while antagonists accelerate epithelial wound healing

Evidence of an endogenous adrenergic network within the corneal epithelium

Christine E. Pullar, Min Zhao, Bing Song, Jin Pu, Brian Reid, Shahed Ghoghawala, Colin McCaig, Roslyn Rivkah Isseroff

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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 β2-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, β-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, β-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 (β-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 β-adrenergic antagonist is blockade of the β2-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.

Original languageEnglish (US)
Pages (from-to)261-272
Number of pages12
JournalJournal of Cellular Physiology
Volume211
Issue number1
DOIs
StatePublished - Apr 2007

Fingerprint

Adrenergic Agonists
Corneal Epithelium
Adrenergic Agents
Wound Healing
Epithelial Cells
Adrenergic Receptors
Adrenergic Antagonists
Epinephrine
Cell Movement
Wounds and Injuries
Repair
Electric fields
Biological Phenomena
Protein Phosphatase 2
Cell Extracts
Catecholamines
Cytoplasm
Enzymes
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

β-adrenergic receptor agonists delay while antagonists accelerate epithelial wound healing : Evidence of an endogenous adrenergic network within the corneal epithelium. / Pullar, Christine E.; Zhao, Min; Song, Bing; Pu, Jin; Reid, Brian; Ghoghawala, Shahed; McCaig, Colin; Isseroff, Roslyn Rivkah.

In: Journal of Cellular Physiology, Vol. 211, No. 1, 04.2007, p. 261-272.

Research output: Contribution to journalArticle

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