Serotonin (5-HT) in Veins: Not All in Vain

Abstract

The circulatory system consists of veins and arteries. Compared with arteries, veins have been neglected in cardiovascular research. Although veins are significantly less muscular than similarly sized arteries, the contribution of veins to cardiovascular homeostasis cannot be left un-noted because veins accommodate 70% of the circulating blood. Circulating blood platelets contain the majority of systemic 5-HT (5-hydroxytryptamine; serotonin). Similar to venous function, the physiological role of 5-HT in the cardiovascular system is not well understood. Here, we present not only a review on 5-HT and veins but ways in which these two topics might intersect in a physiologically relevant manner. Here we show the novel findings that veins exhibit higher amounts of intracellular 5-HT than arteries. Moreover, we also show evidence that, similar to arteries, veins have the ability to uptake 5-HT. In this review, we introduce the venous system as a reservoir for 5-HT in the periphery, suggesting that veins, in addition to arteries, may represent an important target for drugs that interfere with the serotonergic system. In addition, the serotonergic system from synthesis to metabolism, 5-HT receptor activation and venous diseases will also be discussed.Serotonin (5-hydroxytryptamine or 5-HT) has long been the subject of study in many areas of biomedical sciences. Its isolation and characterization was made possible due to the hard work of two independent laboratories more than 60 years ago.In 1937 in Italy, Erspamer and Vially observed that a substance derived from the enterochromaffin cells of the gut caused smooth muscle contraction, especially in the rat uterus. This substance was called enteramine. In 1948 in the United States, M. M. Rapport, A. A. Green, and I. H. Page (Rapport et al., 1948) isolated a compound from beef serum that was able to cause vascular contraction, which they called serotonin. Some years later, enteramine and serotonin were found to be the same substance: 5-hydroxytryptamine (5-HT). The recognition of 5-HT as a neurotransmitter after it was found in mammalian brain brought it into the field of neuroscience. These findings were followed by the proposed role of 5-HT in mental illness (for review, see WhitakerAzmitia, 1999). The involvement of 5-HT in the central nervous system has long been established and, therefore, is beyond the scope of this review.Despite initially being described as a vasoconstrictor, the role of 5-HT in the cardiovascular system is far from being elucidated. A role for 5-HT in the pulmonary circulation has become established in the last past decade. However, sites of 5-HT synthesis in the nonpulmonary peripheral vasculature have not yet been identified. As a consequence, our current understanding is that the systemic vasculature is exposed to

A Serotonergic System in Veins: Serotonin Transporter-Independent Uptake

“…Preliminary data from our laboratory revealed that veins were able to take up 5-HT in a significantly larger amount than arteries (Linder et al, 2007). These novel findings suggest that veins, in addition to platelets, may function as a sink for 5-HT in the cardiovascular system.…”

“…5-HT modifies venous tone through direct interaction with venous 5-HT receptors (Cushing et al, 1994;Watts and Cohen, 1999;Watts, 2005;Linder et al, 2007) and indirectly by modifying sympathetic control of venous motor tone . Thus, it is important to understand how 5-HT is handled by venous tissue, as modification in handling could ultimately affect the actions of 5-HT in veins and therefore blood pressure.…”

Matrix Metalloproteinase-2 and Epidermal Growth Factor are Decreased in Platelets of Alzheimer Patients

“…Platelets are the main source of peripheral serotonin [6,24]. AD has been shown to have increased plasma serotonin levels, which could derive from platelets [25].…”

Supplemental dietary tryptophan modifies behavior, concentrations of salivary cortisol, plasma epinephrine, norepinephrine and hypothalamic 5-hydroxytryptamine in weaning piglets

“…Tryptophan crosses the blood-brainbarrier via transporter proteins and acts as the precursor for 5-hydroxytryptamine (5-HT) synthesis in the serotonergic neurons. The cerebral neurotransmitter 5-HT is essential for aggression inhibition (Nelson and Chiavegatto, 2001) and also regulates sleeping, appetite, mood and behavioral activity (Linder et al, 2007;S eve, 1999). Tryptophan has been shown to affect brain and nervous system function through interference with serotonergic neurotransmission.…”

“…5-HT plays a major role in appetite, behavioral activity and aggression regulatory mechanism. Therefore, tryptophan deficiency leads to intensification of aggressive behaviors in several animal species and humans (Linder et al, 2007;Miczek and Fish, 2005;Miczek et al, 2002).…”