Neuronal nicotinic receptors in non-neuronal cells: new mediators of tobacco toxicity?

The nicotinic acetylcholine receptors are prototypic ionotropic receptors t hat mediate fast synaptic transmission. However, also non-excitable cells, and particularly the tegumental cells that line external and internal body surfaces, express acetylcholine receptors of neuronal type sensitive to nic otine. Bronchial epithelial cells, endothelial cells of blood vessels and s kin keratinocytes express neuronal nicotinic receptors composed of alpha(3) , alpha(5), beta(2) and beta(4) subunits, similar to those expressed in sym pathetic ganglia, and neuronal nicotinic receptors composed of alpha(7) sub units. Neuronal nicotinic receptors in tegumental cells are involved in mod ulating cell shape and motility, and therefore in maintaining the integrity of the surfaces lined by those cells. Neuronal nicotinic receptors in non- neuronal tissues may modulate other functions, including cell proliferation and differentiation. Acetylcholine is synthesized, secreted and degraded b y a variety of cells, including the tegumental cells that express neuronal nicotinic receptors. Thus, acetylcholine may function as a local "hormone" that is able to modulate cell functions that require fast adaptation to new conditions. The presence of neuronal nicotinic receptors sensitive to nico tine in tissues known to be involved in tobacco toxicity, like bronchi and blood vessels, raises the possibility that they mediate some of the toxic e ffects of smoking. (C) 2000 Elsevier Science B.V. All rights reserved.