Abstract
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.
Footnotes
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This work was supported by National Institutes of Health Grant HL81115 (to S.W.W.) and American Heart Association Postdoctoral Fellowship 0725729Z (to A.E.L.).
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.107.135699.
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ABBREVIATIONS: 5-HT, 5-hydroxytryptamine (serotonin); 5-HTP, 5-hydroxytryptophan; TPH, tryptophan hydroxylase; SERT, serotonin transporter; MAO, monoamine oxidase; 5-HIAA, 5-hydroxyindole acetic acid; KO, knockout; WT, wild type; B2m, β-2-microglobulin; PCR, polymerase chain reaction; HPLC, high-performance liquid chromatography; PBS, phosphate-buffered saline; NET, norepinephrine transporter; VC, vena cava; JV, jugular vein; RA, rat aorta; CA, carotid artery; BH4, tetrahydrobiopterin.
- Received December 20, 2007.
- Accepted February 29, 2008.
- The American Society for Pharmacology and Experimental Therapeutics
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