A serotonergic system in veins: serotonin transporter-independent uptake.
We hypothesized that the 5-hydroxytryptamine (5-HT; serotonin) system is present and functional in veins. In vena cava (VC), the presence of the 5-HT synthesis rate-limiting enzyme tryptophan hydroxylase-1 mRNA and accumulation of the 5-HT synthesis intermediate 5-hydroxytryptophan after incubation with tryptophan supported the ability of veins to synthesize 5-HT. The presence of 5-HT and its metabolite 5-hydroxyindole acetic acid was measured by high-performance liquid chromatography in VC and jugular vein (JV), and it was compared with similarly sized arteries aorta (RA) and carotid (CA), respectively. In rats treated with the monoamine oxidase-A (MAO-A) inhibitor pargyline to prevent 5-HT metabolism, basal 5-HT levels were higher in veins than in arteries. 5-HT uptake was observed after exposure to exogenous 5-HT in all vessels. The presence of MAO-A and the 5-HT transporter (SERT) in VC was observed by immunohistochemistry and Western analysis. However, 5-HT uptake was not inhibited by the SERT inhibitors fluoxetine and/or fluvoxamine in VC and JV, as opposed to the inhibition in RA and CA. Moreover, studies performed in VC from mutant rats lacking SERT showed no differences in 5-HT uptake compared with VC from wild type. These data suggest the SERT is not functional under physiological conditions in veins. The differences in 5-HT handling between veins and arteries may represent alternative avenues for targeting the 5-HT system in the peripheral circulation for controlling vascular tone.
Linder
A Elizabeth
AE
Department of Pharmacology and Toxicology, Michigan State University, B445 Life Sciences Bldg., East Lansing, MI 48824, USA. linderau@msu.edu
Ni
Wei
W
Szasz
Theodora
T
Burnett
Robert
R
Diaz
Jessica
J
Geddes
Timothy J
TJ
Kuhn
Donald M
DM
Watts
Stephanie W
SW
D000818:Animals; D030801:Animals, Genetically Modified; D001011:Aorta / Q000378:metabolism; D002339:Carotid Arteries / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007601:Jugular Veins / Q000378:metabolism*; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000235:genetics; D014684:Venae Cavae / Q000378:metabolism*
D012333:RNA, Messenger; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D014365:Tryptophan Hydroxylase; C504570:tph1 protein, rat; D008995:Monoamine Oxidase