β3-Adrenergic receptors mediate choroidal endothelial cell invasion, proliferation, and cell elongation

Jena J. Steinle, David O. Zamora, James (Jim) Rosenbaum, Harris J. Granger

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

β3-Adrenergic receptors have been reported to function primarily in adipose tissues to regulate thermogenesis. In this study, we determined if β-adrenergic receptors are present on human choroidal endothelial cells and examined their ability to promote invasion, proliferation, and/or cell elongation. Using western blotting techniques and assays of cell invasion, cell proliferation, and endothelial cell elongation, we were able to determine that human choroidal endothelial cells do possess all three subtypes of β-adrenergic receptors. Stimulation of the β3-adrenergic receptor with BRL37344, a specific β3-adrenergic receptor agonist, resulted in phosphorylation of Src, Akt, and ERK1/2. BRL37344 treatment also increased choroidal endothelial cell invasion by 103% above control values; the invasion response was inhibited by PP2 (Src inhibitor), LY294002 (PI3K inhibitor), Akt inhibitor (Akt-I), and matrix metalloproteinase 2/9 inhibitor (MMP-I). Invasion was not affected by PD98059 (mek inhibitor) or KT5823 (protein kinase G inhibitor). BRL37344 produced a significant increase in the total elongation of choroidal endothelial cells formed on Matrigel over a 24 hr period. BRL37344 did significantly increase proliferation, although not to the same level as invasion. Stimulation of choroidal endothelial cells with dobutamine to activate β12-adrenergic receptors did not affect invasion, proliferation, or endothelial cell elongation. In conclusion, β3-adrenergic receptors may play a role in choroidal endothelial cell invasion and elongation, while playing a more limited function in regulation of cell proliferation.

Original languageEnglish (US)
Pages (from-to)83-91
Number of pages9
JournalExperimental Eye Research
Volume80
Issue number1
DOIs
StatePublished - Jan 2005

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Adrenergic Receptors
Endothelial Cells
Cell Proliferation
Cyclic GMP-Dependent Protein Kinases
Adrenergic Agonists
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Dobutamine
Thermogenesis
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Protein Kinase Inhibitors
Phosphatidylinositol 3-Kinases
Adipose Tissue
Western Blotting
Phosphorylation

Keywords

  • angiogenesis
  • beta-adrenergic
  • choroid
  • sympathetic

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems

Cite this

β3-Adrenergic receptors mediate choroidal endothelial cell invasion, proliferation, and cell elongation. / Steinle, Jena J.; Zamora, David O.; Rosenbaum, James (Jim); Granger, Harris J.

In: Experimental Eye Research, Vol. 80, No. 1, 01.2005, p. 83-91.

Research output: Contribution to journalArticle

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