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CARDIOVASCULAR

A Serotonergic System in Veins: Serotonin Transporter-Independent Uptake

Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan (A.E.L., W.N., T.S., R.B., J.D., S.W.W.); and John D. Dingell VA Medical Center, Research and Development Service, Detroit, Michigan (T.J.G., D.M.K.)

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.

Address correspondence to: Dr. A. Elizabeth Linder, Department of Pharmacology and Toxicology, Michigan State University, B445 Life Sciences Bldg., East Lansing, MI 48824. E-mail: linderau{at}msu.edu

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				S. W. Watts The beginning of a fantastic, unanswered question: is 5-HT involved in systemic hypertension? Am J Physiol Heart Circ Physiol, September 1, 2008; 295(3): H915 - H916. [Abstract] [Full Text] [PDF]