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.
Liu
Yuan-Sheng
YS
Department of Hematology, First Affiliated Hospital, Shantou University Medical College, Shanton, 515041, People's Republic of China.
Yang
Mo
M
D001792:Blood Platelets / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008533:Megakaryocytes / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D044348:Receptors, Serotonin, 5-HT2 / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D034061:Thrombopoiesis / Q000502:physiology*
D036341:Intercellular Signaling Peptides and Proteins; D044348:Receptors, Serotonin, 5-HT2; D012701:Serotonin; D052247:Nitric Oxide Synthase Type II