PT  - JOURNAL ARTICLE
AU  - A. Elizabeth Linder
AU  - Wei Ni
AU  - Theodora Szasz
AU  - Robert Burnett
AU  - Jessica Diaz
AU  - Timothy J. Geddes
AU  - Donald M. Kuhn
AU  - Stephanie W. Watts
TI  - A Serotonergic System in Veins: Serotonin Transporter-Independent Uptake
AID  - 10.1124/jpet.107.135699
DP  - 2008 Jun 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 714--722
VI  - 325
IP  - 3
4099  - http://jpet.aspetjournals.org/content/325/3/714.short
4100  - http://jpet.aspetjournals.org/content/325/3/714.full
SO  - J Pharmacol Exp Ther2008 Jun 01; 325
AB  - 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. The American Society for Pharmacology and Experimental Therapeutics