Norepinephrine transport by the extraneuronal monoamine transporter in human bronchial arterial smooth muscle cells

Gabor Horvath, Zoltan Sutto, Aliza Torbati, Gregory E. Conner, Matthias Salathe, Adam Wanner

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


Inhaled glucocorticosteroids (GSs) cause acute, α 1-adrenoreceptor (AR)-mediated bronchial vasoconstriction. After release from sympathetic nerves, norepinephrine (NE) must be taken up into cells for deactivation by intracellular enzymes. Because postsynaptic cellular NE uptake is steroid sensitive, GSs could increase NE concentrations at α1-AR, causing vasoconstriction. We therefore evaluated mRNA expression of different NE transporters in human bronchial arterial smooth muscle and pharmacologically characterized NE uptake into these cells. RT-PCR demonstrated mRNA expression of the extraneuronal monoamine transporter (EMT) and organic cation transporter 1 (OCT-1). Fluorometric uptake assay showed time (within minutes)- and concentration-dependent NE uptake by freshly isolated bronchial arterial smooth muscle cells (SMC) with an estimated Km of 240 μM. Corticosterone and O-methylisoprenaline (1 μM each), but not desipramine, inhibited NE uptake, a profile indicative of NE uptake by EMT, but not OCT-1. Budesonide and methylprednisolone inhibited uptake with IC 50 values of 0.9 and 5.6 μM, respectively. Corticosterone's action was reversible and not sensitive to RU-486 (GS receptor antagonist), actinomycin D (transcription inhibitor), or cycloheximide (protein synthesis inhibitor). Corticosterone made membrane impermeant by coupling to BSA also blocked NE uptake. Immunocytochemistry indicated a specific membrane binding site for corticosterone on bronchial arterial SMC. These data demonstrate that although human bronchial arterial SMC express OCT-1 and EMT, EMT is the predominant plasma membrane transporter for NE uptake. This process can be inhibited by GSs, likely via a specific membrane binding site. This non-genomic GS action (increasing NE concentrations at α1-AR) could explain acute bronchial vasoconstriction caused by inhaled GSs.

Original languageEnglish (US)
Pages (from-to)L829-L837
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number4 29-4
StatePublished - Oct 1 2003


  • Budesonide
  • Glucocorticosteroids
  • Non-genomic
  • Plasma membrane binding site
  • Vasoconstriction

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology


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