Effects of antithrombin III (AT III) and Trp49-modified AT III on plasma level of 6-keto-PGF1 alpha in rats.
We evaluated the effect of antithrombin III (AT III) on the plasma level of 6-keto-PGF1 alpha in rats to determine whether AT III may promote the release of prostacyclin (PGl2) from endothelial cells in vivo. The intravenous administration of AT III (250 U/kg) significantly increased the plasma levels of 6-keto-PGF1 alpha, with a peak seen 90 min post-administration. Neither Trp49-modified AT III, which lacks affinity for heparin but retains an inhibitory capacity for thrombin, nor heparin plus AT III, increased the plasma level of 6-keto-PGF1 alpha 90 min after administration. Indomethacin pretreatment inhibited the increase in plasma levels of 6-keto-PGF1 alpha produced by AT III. Observations suggest that AT III may promote the release of PGl2 from endothelial cells by interacting with heparin-like glycosaminoglycans in vivo, consistent with previous observations in cultured endothelial cells.
Uchiba
M
M
Department of Medicine, Kumamoto University Medical School, Japan.
Okajima
K
K
Murakami
K
K
Okabe
H
H
Takatsuki
K
K
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood*; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D000990:Antithrombin III / Q000494:pharmacology*; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D014364:Tryptophan / Q000494:pharmacology*
D000925:Anticoagulants; D016861:Cyclooxygenase Inhibitors; D015842:Serine Proteinase Inhibitors; D015121:6-Ketoprostaglandin F1 alpha; D014364:Tryptophan; D000990:Antithrombin III; D006493:Heparin; D011464:Epoprostenol; D007213:Indomethacin