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

Abstract

The serotonergic system, serotonin (5HT), serotonin transporter (SERT), and serotonin receptors (5HT-x), is an evolutionarily ancient system that has clear physiological advantages to all life forms from bacteria to humans. This review focuses on the role of platelet/plasma serotonin and the cardiovascular system with minor references to its significant neurotransmitter function. Platelets transport and store virtually all plasma serotonin in dense granules. Stored serotonin is released from activated platelets and can bind to serotonin receptors on platelets and cellular components of the vascular wall to augment aggregation and induce vasoconstriction or vasodilation. The vascular endothelium is critical to the maintenance of cardiovascular homeostasis. While there are numerous ligands, neurological components, and baroreceptors that effect vascular tone it is proposed that serotonin and nitric oxide (an endothelium relaxing factor) are major players in the regulation of systemic blood pressure. Signals not fully defined, to date, that direct serotonin binding to one of the 15 identified 5HT receptors versus the transporter, and the role platelet/plasma serotonin plays in regulating hypertension within the cardiovascular system remain important issues to better understand many diseases and to develop new drugs. Also, expanded research of these pathways in lower life-forms may serve as important model systems to further our understanding of the evolution and mechanisms of action of serotonin.