Tetrahydrobiopterin attenuates modulation of platelet 12-lipoxygenase and cyclooxygenase activities by nitric oxide.
Endothelial cells secrete large amounts of 5,6,7,8-tetrahydrobiopterin (BH(4)) in septic conditions. BH(4) is a cofactor for nitric oxide (NO) synthase and an essential regulator of its activity. We recently showed that NO can be a modulator of both platelet 12-lipoxygenase and cyclooxygenase activities. In the present study, we investigated the effect of BH(4) on the activities of 12-lipoxygenase and cyclooxygenase in rabbit platelets. The influence of BH(4) on NO-induced modulation of these enzyme activities was investigated. Exogenous BH(4) did not affect platelet 12-lipoxygenase and cyclooxygenase activities. The modulatory effects of NO on the two enzymatic pathways were reversed by addition of BH(4) but not by reduced glutathione. These results suggest that exogenous BH(4) is not essential for NO synthase activity of platelets, but that it is an important regulator of the action of NO released from other sources on platelet 12-lipoxygenase and cyclooxygenase activities.
Fujimoto
Y
Y
Department of Hygienic Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan. fujimoto@oysun01.oups.ac.jp
Sakuma
S
S
Iba
Y
Y
Sasaki
T
T
Fujita
T
T
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000097:blood; D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000097:blood*; D001095:Arachidonic Acids / Q000097:blood; D001708:Biopterins / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000097:blood; D005978:Glutathione / Q000097:blood; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood*; D011817:Rabbits; D013929:Thromboxane B2 / Q000097:blood; D014226:Triazenes / Q000493:pharmacokinetics
C100973:(1-hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-3-aminopropyl)-3-methyl-1-triazene; D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D005231:Fatty Acids, Unsaturated; D016859:Lipoxygenase Inhibitors; D020030:Nitric Oxide Donors; D014226:Triazenes; D001708:Biopterins; D009569:Nitric Oxide; C008033:12-hydroxy-5,8,10-heptadecatrienoic acid; D013929:Thromboxane B2; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D001092:Arachidonate 12-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; C003402:sapropterin; D005978:Glutathione