Molecular targets for steroids in airway vascular smooth muscle.
The actions of norepinephrine (NE) released from airway sympathetic nerves are partially terminated by the extraneuronal catecholamine uptake. Because various steroid hormones inhibit extraneuronal uptake, it could be responsible for the airway vasoconstriction caused by inhaled glucocorticosteroids (GSs) in vivo. Using bronchial arteries obtained from donor lungs rejected for transplantation, we showed that a plasma membrane-associated transporter is responsible for NE uptake by airway vascular smooth muscle. We identified this transporter, namely the extraneuronal monoamine transporter (EMT), by demonstrating its function and mRNA expression. Furthermore, we showed that the rapid, nongenomic inhibitory GS effect on EMT is likely mediated through the activation of specific K+ channels in the plasma membrane. We believe that our studies identified new molecular targets for GSs in modulating noradrenergic control of airway vascular tone.
Horvath
G
G
Department of Respiratory Medicine, Semmelweis University, Budapest, Hungary. hg2000@freemail.hu
Wanner
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D001665:Binding Sites; D001980:Bronchi / Q000098:blood supply*; D001981:Bronchial Arteries / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003345:Corticosterone / Q000378:metabolism; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins; D027701:Organic Cation Transport Proteins / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013256:Steroids / Q000378:metabolism*; D027981:Symporters / Q000096:biosynthesis / Q000235:genetics; D000099254:Organic Cation Transporter 3
D003345:Corticosterone; D009638:Norepinephrine; D050484:Norepinephrine Plasma Membrane Transport Proteins; D027701:Organic Cation Transport Proteins; D011188:Potassium; D015221:Potassium Channels; D012333:RNA, Messenger; D013256:Steroids; D027981:Symporters; D000099254:Organic Cation Transporter 3; C493227:SLC6A2 protein, human