Immuno-Thrombotic Effects of Platelet Serotonin

Abstract

Platelets transport and store serotonin at a high concentration in dense granules and release it upon activation. Abnormal serotonin concentrations in the blood plasma or increased platelet serotonin release promote the development of thrombosis, sepsis, allergic asthma, myocardial infarction, and stroke. Consequently, experimental data suggest possible benefits of serotonin receptor blockade or inhibition of platelet serotonin uptake in the indicated human diseases. Here, we highlight the current state of basic biological research regarding the role of platelet serotonin in normal and pathophysiological conditions focusing on thrombotic and inflammatory diseases. We also describe the possible clinical applicability of targeting thrombo-immune-modulatory effects of platelet serotonin to treat common health problems.

Cardiovascular serotonergic system: Evolution, receptors, transporter, and function

“…Many different types of immune cells synthesize serotonin and/or transport serotonin via their membrane bound SERT and possess virtually all known serotonin receptors (Herr et al, 2017; Quintero‐Villegas & Valdes‐Ferrer, 2019; Wu et al, 2019). Mammalian platelets contribute to the immune response by direct interactions with some immune cell types and by release of their stored serotonin (Mammadova‐Bach et al, 2017; Ponomarev, 2018; Schoenichen et al, 2019). The synthesis, storage, and functions of serotonin in the GI tract and a connection between the GI tract and the brain has been reviewed (Banskota et al, 2019; Camilleri, 2009; Del Colle et al, 2020; Gershon & Tack, 2007).…”

“…Serotonin, or 5‐hydroxytryptamine (5‐HT) is synthesized from the amino acid, l ‐tryptophan. About 95% of the serotonin in the mammalian system is synthesized in the enterochromaffin cells in the gastrointestinal (GI) tract and 5% in the brain (Camilleri, 2009; Mammadova‐Bach et al, 2017). Serotonin is a paracrine messenger and a neurotransmitter in the gut where it plays an essential role in modulating gut motility, sensation, and secretion.…”

“…All normal and pathological functions of serotonin in vertebrates and invertebrates require its interaction with a specific serotonin receptor, 5‐HTx. There are at least 15 known mammalian serotonin receptors that fall into a superfamily of 7 receptor types (Frazer & Hensler, 1999; Gershon & Tack, 2007; Mammadova‐Bach et al, 2017). The biology, genetics and pharmacology of the serotonin receptors have been reviewed elsewhere (Boess & Martin, 1994; Frazer & Hensler, 1999; Hannon & Hoyer, 2008; Hoyer et al, 1994, 2002; Nichols & Nichols, 2008; Pytliak et al, 2011; Saudou & Hen, 1994) and will not be addressed in this review except where it pertains to function within the cardiovascular system.…”

Effects of Nutrients on Platelet Function: A Modifiable Link between Metabolic Syndrome and Neurodegeneration?

“…Dietary intake of the precursors of these amines could affect platelet aggregation and subsequently even neurological function. In more detail, serotonin is synthesized from tryptophan to 5-hydroxy-tryptophan by either tryptophan hydroxylase-1 (brain, 5%) or -2 (periphery, mainly enterochromaffin cells in the gastrointestinal tract 95%) [137]. Diets enriched with tryptophan (4 and 10 g/kg) enhanced ADP-induced platelet aggregation, most likely via the (increased) synthesis of serotonin, and may thereby contribute to atherosclerotic risk [138].…”

Tryptophan and Membrane Mobility as Conditioners and Brokers of Gut–Brain Axis in Depression

“…In addition, the majority of peripheral 5-HT is stored in platelets. On the other hand, platelets do not synthesize 5-HT, but they adsorb it from plasma through the 5-HT transporter and release it during their activation [21]. Actually, the function of 5-HT in platelets is not clear yet; studies suggest that it is important for the serotonylation of the proteins necessary in platelet aggregation [22].…”