Endothelial cell nicotinic acetylcholine receptor (nAChR) (nAChR)

Endothelial cell nicotinic acetylcholine receptors (nAChRs) are a specialized population of ligand-gated ion channels located on the surface of vascular endothelial cells, where they serve as critical regulators of angiogenesis, vascular permeability, and inflammatory responses [1, 4]. Although endothelial cells express a variety of nAChR subunits, including α3, α4, α5, α9, and β2, the homomeric α7-nAChR subtype is the most extensively characterized for its role in mediating the pro-angiogenic effects of both endogenous acetylcholine and exogenous nicotine [2, 8]. Upon activation by an agonist, these receptors undergo a conformational change that opens a cation-selective pore, allowing for the influx of calcium ions and the subsequent activation of intracellular signaling cascades such as the PI3K/Akt, MAPK/ERK, and eNOS pathways [2, 6, 12]. These pathways collectively drive essential angiogenic processes, including endothelial cell proliferation, migration, and tube formation [2, 5]. In clinical medicine, endothelial nAChRs are significant due to their involvement in both physiological and pathological conditions. They are essential for normal wound healing and the development of collateral circulation in ischemic tissues; however, their overactivation is linked to the progression of tobacco-related diseases, such as tumor growth via enhanced tumor angiogenesis and the destabilization of atherosclerotic plaques through neovascularization [3, 7, 9]. Consequently, these receptors are viewed as dual-purpose therapeutic targets: nAChR antagonists are being explored to inhibit pathological angiogenesis in cancer and retinopathy, while selective agonists are investigated for their potential to promote revascularization in cardiovascular diseases [4, 12]. Common pharmacological tools used to study or target these receptors include agonists like nicotine, varenicline, and GTS-21, as well as antagonists such as mecamylamine and the α7-selective toxin α-bungarotoxin [4, 11].

Other names

Non-neuronal nicotinic acetylcholine receptorVascular nicotinic acetylcholine receptorEndothelial nAChRAlpha-7 nicotinic acetylcholine receptor (endothelial subtype)

Agonists bind to the extracellular domain of the pentameric receptor, inducing a conformational change that opens a central cation-selective pore. This allows the influx of calcium (Ca2+) and sodium (Na+) ions, which depolarizes the cell and activates intracellular signaling cascades, including the activation of endothelial nitric oxide synthase (eNOS) and various protein kinases such as PI3K/Akt and MAPK/ERK that drive angiogenic processes [2, 4, 6].