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 by 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 they are sensitive to nicotine. We demonstrate here that endothelial cells that line blood vessels express functional nAChRs. Their structure and ion-gating properties are similar to those of the nAChRs expressed by ganglionic neurons and by skin keratinocytes and bronchial epithelial cells. In situ hybridization experiments using primary cultures of endothelial cells from human aorta demonstrated the presence in these cells of the subunits believed to contribute to ganglionic ACh receptors (AChRs) of the alpha3 subtype: alpha3, alpha5, beta2 and beta4. Binding of radiolabeled epibatidine-a high-affinity specific ligand of certain neuronal AChRs, including the alpha3 subtypes-revealed the presence of approximately 900 specific binding sites per cell. We assessed the presence of functional AChRs by patch-clamp experiments. Cultured human endothelial cells express ion channels that are opened by (+)-anatoxin-a and are blocked by dihydro-beta-erythroidine. These are specific agonist and antagonist, respectively, of neuronal AChRs of the alpha3 subtype. The ion-gating properties of the endothelial AChRs were similar to those of neuronal ganglionic AChRs. The presence of AChRs sensitive to nicotine in endothelial cells may be related to the toxic effects of nicotine on the vascular system.
Macklin
K D
KD
Department of Biochemistry, University of Minnesota, St. Paul, Minnesota, USA.
Maus
A D
AD
Pereira
E F
EF
Albuquerque
E X
EX
Conti-Fine
B M
BM
D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000737:chemistry*; D006801:Humans; D017403:In Situ Hybridization; D015640:Ion Channel Gating; D018408:Patch-Clamp Techniques; D011725:Pyridines / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011978:Receptors, Nicotinic / Q000032:analysis* / Q000235:genetics / Q000502:physiology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D011725:Pyridines; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; C082748:epibatidine