The serotonin transporter is present and functional in peripheral arterial smooth muscle.
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.
Ni
Wei
W
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824-1317, USA.
Thompson
Janice M
JM
Northcott
Carrie A
CA
Lookingland
Keith
K
Watts
Stephanie W
SW
D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology*; D003900:Desoxycorticosterone / Q000633:toxicity; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology*; D026901:Membrane Transport Proteins; D008638:Mesenteric Arteries / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D012701:Serotonin; D003900:Desoxycorticosterone