Up-regulation of thrombomodulin by activation of histamine H1-receptors in human umbilical-vein endothelial cells in vitro.
Previous reports demonstrated that the expression of thrombomodulin (TM) in endothelial cells was modulated by various agents. Although TM was down-regulated by endotoxin or cytokines, up-regulation of TM was accomplished when endothelial cells were stimulated with unphysiologically high concentrations of cyclic AMP derivatives or tumour-promoting phorbol esters. We investigated the expression of TM in human umbilical-vein endothelial cells (HUVECs) by physiological substances that can be released into the bloodstream. Histamine (0.1-10 microM, 1-48 h) increased TM activity, TM antigen in cell lysates and TM mRNA levels, but 5-hydroxytryptamine and bradykinin had no effect. Enhancement of TM activity by histamine was completely blocked by the H1-selective antagonist pyrilamine, whereas the H2-antagonist cimetidine had no effect, showing that histamine up-regulates TM activity via H1-receptors on HUVECs. Enhanced TM activity by histamine and the resultant increase in protein C activation might play a role in a feedback regulation for prevention of vascular thrombosis.
Hirokawa
K
K
First Department of Medicine, Tokyo Medical and Dental University, Japan.
Aoki
N
N
D000941:Antigens / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D011486:Protein C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000502:physiology*; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000502:physiology*; D018179:Receptors, Thrombin; D014471:Umbilical Veins; D015854:Up-Regulation
D000941:Antigens; D011486:Protein C; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011969:Receptors, Histamine H1; D018179:Receptors, Thrombin; D006632:Histamine; D001241:Aspirin; D007213:Indomethacin