Abstract
Cigarette smoking is one of the major causes of coronary heart disease with a thirty percent mortality rate in the United States. Cigarette smoking acting on the central nervous system (CNS) to stimulate the sympathetic nervous system (SNS) through, which facilitates the secretion of serotonin (5-HT) and catecholamines to supraphysiological levels in blood. The enhanced levels of 5-HT and catecholamines in smokers’ blood are associated with increases in G protein-coupled receptor signaling and serotonylation of small GTPases, which in turn lead to remodeling of cytoskeletal elements to enhance granule secretion and promote unique expression of sialylated N-glycan structures on smokers’ platelets. These mechanisms enhance aggregation and adhesion of smokers’ platelets relative to those of non-smokers. This review focuses on the known mechanisms by which 5-HT and SERT, in coordinated signaling with catecholamines, impacts cigarette smokers’ platelet biology.
Highlights
Serotonin (5-HT) is secreted from the enterochromaffin cells of the intestine to the blood and taken into the platelets by a specific transporter, SERT (SLC6A4) via a saturable reuptake mechanism (Rudnick, 1977; Lesch et al, 1993; McNicol and Israels, 1999; McNicol and Israels, 2003)
Vesicular monoamine transporter (VMAT) on the dense granules takes free 5-HT from the platelet cytoplasm into the dense granule which is sequestered there to millimolar concentrations, while free concentrations in the blood are in the low nanomolar range (McNicol and Israels, 2003; Brenner et al, 2007)
We reported several studies related with the impact of sympathetic nervous system (SNS)-activated secretion of 5-HT into the blood (Brenner et al, 2007; Mercado and Kilic, 2010; Fraer and Kilic, 2015; Lowery et al, 2017), on platelet aggregation via activation of the 5-HT receptor (5-HT2A) (Ziu et al, 2014), on the secretion of granules as a result of serotonylation of small GTPases (Ahmed et al, 2008; Mercado et al, 2011; Ziu et al, 2012; Li et al, 2016), alteration of the cytoskeletal network (Ahmed et al, 2009; Li et al, 2016), and alteration of the structure and composition of glycans on the surface of mouse platelets (Mercado et al, 2013)
Summary
Serotonin (5-HT) is secreted from the enterochromaffin cells of the intestine to the blood and taken into the platelets by a specific transporter, SERT (SLC6A4) via a saturable reuptake mechanism (Rudnick, 1977; Lesch et al, 1993; McNicol and Israels, 1999; McNicol and Israels, 2003). Studies in the platelets of mice lacking the gene for tryptophan hydroxylase (TPH1), the rate-limiting enzyme in the synthesis of 5-HT in peripheral cells, demonstrated that intracellular 5-HT acts on the exocytosis of the dense and α-granules during platelet activation (Walther et al, 2003; Ziu et al, 2012, 2014; Lowery et al, 2017) These studies in isolated platelets indicated that 5-HT-stimulation accelerated the exocytosis of granules, which secrete their contents, 5-HT, ADP, and procoagulant molecules, such as fibrinolytic regulators, growth factors, chemokines, immunologic modulators, P-selectin, von Willebrand factor, thrombospondin, fibrinogen, and fibronectin (Shirakawa et al, 2000; Walther et al, 2003; Ziu et al, 2012; Lowery et al, 2017). The main goal of this review is to summarize a novel mechanism by which 5-HT and SERT in coordination with catecholamines impact cigarette smokers’ platelet biology
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
