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The Uptake of Norepinephrine by Vascular Smooth Muscle Cells
Author(s) -
Johnson Kyle B,
Watts Stephanie W
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1083.7
Subject(s) - norepinephrine , vascular smooth muscle , chemistry , smooth muscle , medicine , cardiology , neuroscience , biology , dopamine
Traditionally, norepinephrine (NE) is thought to elicit its effects by interacting with adrenergic receptors. Our lab recently described another way that NE may propagate a biological signal, by acting as a substrate for transglutaminases. For this modification to be physiologically relevant, NE must be inside of the cell. We hypothesized that vascular smooth muscle cells (VSMCs) take up NE via the NE transporter (NET). Western analysis showed that NET was present in whole tissue and cultured VSMC homogenates from rat aorta and vena cava tissues. Immunocytochemical staining for NET in cultured and freshly dissociated VSMCs showed that NET was present in these VSMCs, but not necessarily located on the cell membrane. The ability of VSMCs to take up NE was assessed in the presence of vehicle or 1 μM nisoxetine (NET inhibitor). Uptake by VSMCs was first detected when 10 −7 M NE was added to cells (vehicle = 1.2 ± 0.3 μg NE/ng of protein; 10 −7 NE = 4.3 ± 0.9 μg NE/ng of protein, p<0.05); this was significantly elevated at 10 −5 M NE (361.8 ± 43 μg NE/ng of protein, p<0.05). Nisoxetine slightly but significantly reduced uptake of NE when 10 −6 and 10 −5 M NE was added (10 −6 NE = 69.2 ± 0.6; 10 −5 NE = 82 ± 13% NE uptake versus vehicle treated, p<0.05). These results suggest that VSMCs are able to take up exogenous NE and that the NET is present in VSMCs, but may not be located solely on the membrane. Supported by NIH P01 HL70687.