Human bronchial epithelial and endothelial cells express alpha 7 nicotinicacetylcholine receptors

The epithelial or endothelial cells that line the human bronchi and the aor ta express nicotinic acetylcholine receptors (nAChRs) of alpha3 subtypes. W e report here that human bronchial epithelial cells (BEC) and aortic endoth elial cells (AEC) express also the nAChR alpha7 subunit, which forms functi onal nAChRs. Polymerase chain reaction and in situ hybridization experiment s detected alpha7 subunit mRNA in cultured human BEC and AEC and in section s of rat trachea. The binding of radiolabeled a-bungarotoxin revealed a few thousand binding sites per cell in cultured human BEC and human and bovine AEC. Western blot and immunohistochemistry experiments demonstrated that c ultured BEC and AEC express a protein(s) recognized by anti-alpha7 antibodi es. Whole-cell patch-clamp studies of cultured human BEC demonstrated the p resence of fast-desensitizing currents activated by choline and nicotine th at were blocked reversibly by methyllycaconitine (1 nM) and irreversibly by a-bungarotoxin (100 nM), consistent with the expression of functional alph a7 nAChRs. In some cells, choline activated also slowly decaying currents, confirming previous reports that BEC express functional alpha3 beta4 nAChRs . Exposure of cultured BEC to nicotine (1 muM) for 3 days up-regulated func tional alpha7 and alpha3 nAChRs, as indicated by the increased number of ce lls responding to acetylcholine and choline, with both fast-desensitizing c urrents, which were blocked irreversibly by alpha -bungarotoxin, and with s lowly desensitizing currents, which are alpha -bungarotoxin-insensitive cur rents. The presence of alpha7 nAChRs in BEC and AEC suggests that some toxi c effects of tobacco smoke could be mediated through these nicotine-sensiti ve receptors.