Heparin-like glycosaminoglycan is a receptor for antithrombin III-dependent but not for thrombin-dependent prostacyclin production in human endothelial cells.
Antithrombin III (ATIII) induced a marked increase in prostacyclin (PGI2) release from cultured human umbilical vein endothelial cells (HUVEC) after incubation for more than 2 hr and the induction continued for 8 hr, while thrombin induced the increase within 10 min. ATIII-dependent production of PGI2 was abolished by addition of heparin, but pretreatment of HUVEC with polyclonal antibody against thrombomodulin could not prevent the PGI2 productions by ATIII and thrombin. ATIII-dependent PGI2 production was significantly inhibited by pretreatment of HUVEC with beta-D-xylosides or heparitinase, though neither pretreatment affected thrombin-induced PGI2 production. After treatment of HUVEC with 1 micrograms/ml cycloheximide. ATIII-dependent PGI2 production was completely abolished. These results indicate that the mechanism of the induction of PGI2 production by ATIII involves heparin-like glycosaminoglycans on HUVEC and the stimulation of synthesis of a protein related to PGI2 production. The ATIII-induced PGI2 production is very different from that induced by thrombin.
Horie
S
S
Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
Ishii
H
H
Kazama
M
M
D000911:Antibodies, Monoclonal; D000990:Antithrombin III / Q000502:physiology*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis*; D006025:Glycosaminoglycans / Q000502:physiology*; D006027:Glycosides / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D011133:Polysaccharide-Lyases / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000502:physiology; D018179:Receptors, Thrombin; D013917:Thrombin / Q000502:physiology*
D000911:Antibodies, Monoclonal; D006025:Glycosaminoglycans; D006027:Glycosides; D011956:Receptors, Cell Surface; D018179:Receptors, Thrombin; C010807:xylosides; D000990:Antithrombin III; D006493:Heparin; D003513:Cycloheximide; D011464:Epoprostenol; D013917:Thrombin; D011133:Polysaccharide-Lyases; C021349:heparitinsulfate lyase