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Published on: August 11, 2021
The serotonin transporter is present and functional in peripheral arterial smooth muscle
Wei Ni1, Janice M Thompson, Carrie A Northcott
1Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824-1317, USA.
Abstract:
We tested the hypothesis that the 5-HT transporter (5-HTT) is present and functional in peripheral arterial smooth muscle. In aorta and mesenteric resistance arteries, real time RT-PCR and western analyses indicated the presence of 5-HTT mRNA and a 74 kDa 5-HTT protein. Immunohistochemistry localized the transporter to smooth muscle and endothelial cells. 5-HT and the metabolite 5-hydroxyindole acetic acid (5-HIAA) were detected in aorta, carotid, and superior mesenteric arteries using HPLC; the MAOA inhibitor pargyline significantly increased (over 400%) arterial 5-HT concentration. 5-HT was taken up by arteries in a time-dependent manner and uptake was independent of the endothelium, sympathetic nerves, and norepinephrine transporter. 5-HT-induced contraction of normal aorta was potentiated by the 5-HTT inhibitor fluvoxamine. A change in arterial 5-HTT function occurs in deoxycorticosterone (DOCA)-salt hypertension as the potency and threshold of 5-HT in contracting aorta from the DOCA-salt rat was increased by fluoxetine and fluvoxamine (1 micromol/L; DOCA fluvoxamine -log EC50 [mol/L] = 6.85 +/- 0.08, DOCA-control = 6.44 +/- 0.08); expression of transporter was significantly increased in aorta of DOCA salt rats (145% Sham). These studies show for the first time the presence of the 5-HTT in peripheral arterial smooth muscle and raise the question as to the function of the 5-HTT in regulating peripheral effects of 5-HT.
Insights
The serotonin transporter (5-HTT) is present and functional in peripheral arteries, impacting blood vessel contraction. Its expression and function are altered in deoxycorticosterone-salt hypertension.
Area of Science:
- Cardiovascular Biology
- Neuropharmacology
- Molecular Medicine
Background:
- The role of the serotonin transporter (5-HTT) in peripheral arteries is largely unknown.
- Serotonin (5-HT) influences vascular tone, but its transport mechanisms in arterial smooth muscle require elucidation.
Purpose of the Study:
- To determine if the 5-HTT is present and functional in peripheral arterial smooth muscle.
- To investigate the role of 5-HTT in regulating arterial smooth muscle function and its potential involvement in hypertension.
Main Methods:
- Real-time RT-PCR and Western blot analysis to detect 5-HTT mRNA and protein.
- Immunohistochemistry to localize 5-HTT expression.
- High-performance liquid chromatography (HPLC) to measure 5-HT levels.
- Functional assays measuring 5-HT-induced arterial contraction and 5-HT uptake.
Main Results:
- 5-HTT mRNA and a 74 kDa protein were detected in aorta and mesenteric arteries, localized to smooth muscle and endothelial cells.
- Arteries exhibited time-dependent 5-HT uptake, independent of endothelium and nerves.
- 5-HTT inhibition potentiated 5-HT-induced aortic contraction.
- In deoxycorticosterone-salt hypertension, 5-HTT function was altered, and transporter expression significantly increased in aortic tissue.
Conclusions:
- The 5-HTT is present and functional in peripheral arterial smooth muscle.
- Arterial 5-HTT plays a role in regulating peripheral 5-HT effects and is altered in DOCA-salt hypertension, suggesting a potential contribution to the disease pathology.
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