The existence of a local 5-hydroxytryptaminergic system in peripheral arteries

Br J Pharmacol. 2008 Jun;154(3):663-74. doi: 10.1038/bjp.2008.111. Epub 2008 Apr 14.


Background and purpose: 5-HT is a vasoconstrictor exhibiting enhanced effects in systemic arteries from subjects with cardiovascular disease. The effect of endogenous 5-HT on arteries is controversial, because the concentration of free circulating 5-HT is low and a 5-hydroxytryptaminergic system has not been identified in peripheral arteries. We hypothesized that a local 5-hydroxytryptaminergic system (including 5-HT synthesis, metabolism, uptake and release) with physiological function exists in peripheral arteries.

Experimental approach: The presence of key components of a 5-hydroxytryptaminergic system in rat aorta and superior mesenteric artery was examined using western blot analyses, immunohistochemistry and immunocytochemistry. The function of the rate-limiting enzyme in 5-HT biosynthesis, tryptophan hydroxylase (TPH), and 5-HT transporter was tested by measuring enzyme activity and 5-HT uptake, respectively. Isometric contraction of arterial strips was used to demonstrate the function of released endogenous 5-HT in arterial tissues.

Key results: mRNA for TPH-1 was present in arteries, with low levels of TPH protein and TPH activity. Expression and function of MAO A (5-HT metabolizing enzyme) was supported by immunohistochemistry, western analyses and the elevation of concentrations of 5-hydroxyindoleacetic acid (5-HT metabolite) after exposure to exogenous 5-HT. The 5-HT transporter was localized to the plasma membrane of freshly isolated aortic smooth muscle cells. Peripheral arteries actively took up 5-HT in a time-dependent and 5-HT transporter-dependent manner. The 5-HT transporter substrate, (+)-fenfluramine, released endogenous 5-HT from peripheral arteries, which potentiated noradrenaline-induced arterial contraction.

Conclusions and implications: This study revealed the existence of a local 5-hydroxytryptaminergic system in peripheral arteries.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Aorta, Thoracic / metabolism*
  • Blotting, Western
  • Gene Expression
  • Immunohistochemistry
  • Isometric Contraction
  • Male
  • Mesenteric Artery, Superior / metabolism*
  • Monoamine Oxidase / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / metabolism*
  • Serotonin Plasma Membrane Transport Proteins / metabolism
  • Time Factors
  • Tryptophan Hydroxylase / metabolism


  • RNA, Messenger
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin
  • Tryptophan Hydroxylase
  • tph1 protein, rat
  • Monoamine Oxidase