Beta 3-adrenergic receptors regulate retinal endothelial cell migration and proliferation.
Sympathetic nerves may play a role in vascular disorders of the eye. In the present study, we hypothesized that activation of beta3-adrenergic receptors on retinal endothelial cells would promote migration and proliferation of these cells, two markers of an angiogenic phenotype. We show, for the first time, expression of beta3-adrenergic receptors on cultured retinal endothelial cells. Activation of these receptors with BRL37344, a specific beta3-adrenergic receptor agonist, promoted migration that was blocked by inhibitors of phosphatidylinositol 3-kinase (PI3K), the mitogen activated protein kinase component MEK, and matrix metalloproteinases (MMPs) 2 and 9. BRL37344 stimulated proliferation, which could be blocked by inhibitors of Src, PI3K, and MEK. These cells also express the beta1-adrenergic receptor with no beta2-adrenergic receptor expression observed. Stimulation of the beta1-adrenergic receptor with xamoterol, a specific partial agonist, did not promote proliferation or migration. These results support the hypothesis that beta3-adrenergic receptors play a role in proliferation and migration of cultured human retinal endothelial cells.
Steinle
Jena J
JJ
Department of Medical Physiology, College of Medicine, The Texas A&M University System Health Science Center, Temple, Texas 76504, USA. jsteinle@tamu.edu
Booz
George W
GW
Meininger
Cynthia J
CJ
Day
Jonathan N E
JN
Granger
Harris J
HJ
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D004983:Ethanolamines / Q000494:pharmacology; D006801:Humans; D009389:Neovascularization, Pathologic / Q000378:metabolism; D010766:Phosphorylation; D011412:Propanolamines / Q000494:pharmacology; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism*; D012160:Retina / Q000166:cytology* / Q000378:metabolism; D014316:Tritium
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D011412:Propanolamines; D018342:Receptors, Adrenergic, beta-1; D022702:Receptors, Adrenergic, beta-3; D014316:Tritium; C057368:BRL 37344; C033394:CGP 12177