The immunomodulator FTY720 is phosphorylated and released from platelets.
The novel immunomodulator FTY720 causes lymphocytes from peripheral blood to accumulate in lymphoid tissues. In vivo, FTY720 is phosphorylated to FTY720-P, which binds to the sphingosine 1-phosphate receptor S1P(1). So far, it has been unclear where FTY720-P is produced. We demonstrate that platelets efficiently convert FTY720 to FTY720-P and release it into the extracellular space. This release is mostly independent of platelet activation, but is slightly increased upon thrombin stimulation. These results suggest that platelets are a major source of plasma FTY720-P, and that FTY720-P release is mediated by two different transporters.
Anada
Yoshihiro
Y
Laboratory of Biomembrane and Biofunctional Chemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo, Nishi 6-choume, Kita-ku, Sapporo 060-0812, Japan.
Igarashi
Yasuyuki
Y
Kihara
Akio
A
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000494:pharmacology*; D008246:Lysophospholipids / Q000378:metabolism; D008297:Male; D010766:Phosphorylation; D010949:Plasma / Q000187:drug effects / Q000378:metabolism; D011355:Prodrugs / Q000494:pharmacology*; D011409:Propylene Glycols / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000494:pharmacology
D007166:Immunosuppressive Agents; D008246:Lysophospholipids; D011355:Prodrugs; D011409:Propylene Glycols; C060506:sphingosine 1-phosphate; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine