The effect of 5-hydroxtryptamine on the regulation of megakaryocytopoiesis

5-Hydroxtryptamine (5-HT, serotonin) has been recognized not only as a neurotransmitter and vasoactive agent, but also as a growth factor. 5-HT mainly binds to 5-HT2 receptors or 5-HT1 receptors on cell surfaces to stimulate cell proliferation through Ras or MAPK (mitogen-activated protein kinase) pathways in many cell types. It has been reported that 5-HT stimulates megakaryocytopoiesis via 5-HT receptors (5-HTR). The possible mechanism by which 5-HT regulates the proliferation and differentiation of megakaryocytes (MK) is discussed in this review article. In early stages of megakaryocytopoiesis, 5-HT may bind to 5-HT2B receptors on MK to promote their proliferation and differentiation. In the late stages, 5-HT may be involved in platelet release by inducing nitric oxide (NO) synthesis via 5-HT2A receptors. 5-HT can also antagonize the apoptotic effect induced by thrombospondin-1 (TSP-1) which is a platelet alpha-granule protein and has synergic effects with platelet-derived growth factor (PDGF) to enhance MK proliferation. Therefore, 5-HT is likely to be an important substance in the feedback regulation of thrombopoiesis.