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

33 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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