Research Articles
The neurotransmitter dopamine modulates vascular permeability in the endothelium
Authors:
- Resham BhattacharyaEmail Resham Bhattacharya
- Sutapa Sinha
- Su-Ping Yang
- Chittaranjan Patra
- Shamit Dutta
- Enfeng Wang
- Debabrata Mukhopadhyay
Abstract
Background: Vascular permeability factor/Vascular endothelial growth factor (VPF/VEGF), a multifunctional cytokine, is a potent inducer of vascular permeability, an important early step in angiogenesis. It is known that the neurotransmitter dopamine can inhibit VPF/VEGF mediated angiogenesis, in particular microvascular permeability, but the effectors of this action remain unclear.
Results: Here, we define the signaling pathway modulated by dopamine that inhibits VPF/VEGF induced vascular permeability in endothelial cells. Signals from VPF/VEGF lead to changes in the phosphorylation of tight junction protein zonula occludens (ZO-1) and adherens junction proteins like VE-cadherin and associated catenins, thus weakening endothelial cell-cell adhesion and increasing vascular permeability. We found VEGF receptor-2 (VEGFR-2) to be part of a multiprotein complex involving ZO-1, VE-cadherin and β-catenin. VPF/VEGF induced phosphorylations of VE-cadherin, β-catenin and ZO-1 were inhibited by dopamine treatment. Association of occludin with ZO-1 and ZO-1 with VE-cadherin were significantly inhibited by dopamine in VEGF treated cells. Furthermore, we identified Src as an important target for dopamine-mediated inhibition of VPF/VEGF induced permeability.
Conclusion: Taken together, our results provide molecular insights of dopamine function in the vascular endothelium and suggest a central role of Src in regulating key molecules that control vascular permeability.
- Year: 2008
- Volume: 3
- Page/Article: Art. 14
- DOI: 10.1186/1750-2187-3-14
- Submitted on 2 Jun 2008
- Accepted on 28 Jul 2008
- Published on 28 Jul 2008
- Peer Reviewed