1. The existence of a local 5-hydroxytryptaminergic system in peripheral arteries.
- Author
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Ni, W., Geddes, T. J., Priestley, J. R. C., Szasz, T., Kuhn, D. M., and Watts, S. W.
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SEROTONIN , *VASCULAR smooth muscle , *TRYPTOPHAN , *MONOAMINE oxidase , *ARTERIES , *VASOCONSTRICTORS , *RNA metabolism , *ANIMAL experimentation , *GENE expression , *IMMUNOHISTOCHEMISTRY , *MEMBRANE proteins , *MESENTERIC artery , *MOLECULAR structure , *MUSCLE contraction , *OXIDOREDUCTASES , *RATS , *RESEARCH funding , *TIME , *WESTERN immunoblotting , *THORACIC aorta - Abstract
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.British Journal of Pharmacology (2008) 154, 663–674; doi:10.1038/bjp.2008.111; published online 14 April 2008 [ABSTRACT FROM AUTHOR]
- Published
- 2008
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