Role of Non-neuronal Nicotinic Acetylcholine Receptors in Angiogenesis Modulation

  • Shaker A. Mousa
  • Hugo R. Arias
  • Paul J. Davis


Angiogenesis is a critical physiological process for cell survival and development. Endothelial cells, necessary for the course of angiogenesis, express several non-neuronal nicotinic acetylcholine receptors (AChRs). The most important functional non-neuronal AChRs are homomeric α7 AChRs and several heteromeric AChRs formed by a combination of α3, α5, β2, and β4 subunits, including α3β4-containing AChRs. In endothelial cells, α7 AChR stimulation indirectly triggers the activation of the integrin αvβ3 receptor and an intracellular MAP kinase (ERK) pathway that mediates angiogenesis. Non-selective cholinergic agonists such as nicotine have been shown to induce angiogenesis, enhancing tumor progression. Moreover, α7 AChR selective antagonists such as α-bungarotoxin and methyllycaconitine as well as the nonspecific antagonist mecamylamine have been shown to inhibit endothelial cell proliferation and ultimately blood vessel formation. Exploitation of such pharmacologic properties can lead to the discovery of new specific cholinergic antagonists as anti-cancer therapies. Conversely, the pro-angiogenic effect elicited by specific agonists can be used to treat diseases that respond to revascularization such as diabetic ischemia and foot ulcer, as well as to accelerate wound-healing. In this chapter we discuss the pharmacological evidence supporting the importance of non-neuronal AChRs in angiogenesis. We also explore potential intracellular mechanisms by which α7 AChR activation mediates this vital cellular process.


Vascular Endothelial Growth Factor Vascular Endothelial Growth Factor Expression Choroidal Neovascularization Vascular Endothelial Growth Factor Inhibitor AChR Subunit 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.







nicotinic acetylcholine receptor


protein kinase B


brain-derived neurotrophic factor


basic fibroblast growth factor


chorioallantoic membrane








endothelial cell


epidermal growth factor receptor


extracellular signal-regulated kinase


fibroblast growth factor


FMS-related tyrosine kinase-1


hypoxia-inducible factor-1


IκBα kinase




mitogen-activated protein kinase


MAPK/ERK kinase kinase-1


matrix metalloproteinase


nuclear factor-κB


nitric oxide


non-small cell lung carcinoma


platelet-derived growth factor


platelet-derived growth factor receptor


phosphatidylinositol 3′-kinase


retinoblastoma protein


Src kinase


transforming growth factor-α


transforming growth factor-β


tumor necrosis factor-α


vascular endothelial growth factor


vascular endothelial growth factor receptor


X-linked inhibitor of apoptosis


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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Shaker A. Mousa
    • 1
  • Hugo R. Arias
    • 2
  • Paul J. Davis
    • 3
    • 4
  1. 1.The Pharmaceutical Research Institute at Albany College of Pharmacy and Health SciencesRensselaerUSA
  2. 2.Department of Medical Education, College of MedicineCalifornia North State UniversityElk GroveUSA
  3. 3.The Pharmaceutical Research Institute at Albany College of Pharmacy and Health Sciences AlbanyRensselaerUSA
  4. 4.Department of MedicineAlbany Medical CenterAlbanyUSA

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