HUMAN VASCULAR ENDOTHELIAL-CELLS EXPRESS FUNCTIONAL NICOTINIC ACETYLCHOLINE-RECEPTORS

ACh receptors sensitive to nicotine (nAChR) are present in human skin keratinocytes and in bronchial epithelial cells. They are stimulated b y ACh secreted by the same cells that express them, and they modulate cell motility and shape. A variety of non-neuronal tissues, including endothelial cells, synthesize ACh, which raises the possibility that t hey are sensitive to nicotine. We demonstrate here that endothelial ce lls that line blood vessels express functional nAChRs. Their structure and ion-gating properties are similar to those of the nAChRs expresse d by ganglionic neurons and by skin keratinocytes and bronchial epithe lial cells. In situ hybridization experiments using primary cultures o f endothelial cells from human aorta demonstrated the presence in thes e cells of the subunits believed to contribute to ganglionic ACh recep tors (AChRs) of the alpha 3 subtype: alpha 3, alpha 5, beta 2 and beta 4. Binding of radiolabeled epibatidine-a high-affinity specific ligan d of certain neuronal AChRs, including the alpha 3 subtypes-revealed t he presence of approximately 900 specific binding sites per cell. We a ssessed the presence of functional AChRs by patch-clamp experiments. C ultured human endothelial cells express ion channels that are opened b y (+)-anatoxin-a and are blocked by dihydro-beta-erythroidine. These a re specific agonist and antagonist, respectively, of neuronal AChRs of the alpha 3 subtype. The ion-gating properties of the endothelial ACh Rs were similar to those of neuronal ganglionic AChRs. The presence of AChRs sensitive to nicotine in endothelial cells may be related to th e toxic effects of nicotine on the vascular system.