The mechanism of the inhibitory effect of proteinase inhibitors on platelet aggregation and cellular synthesis of prostaglandins. I. The effect on the release of arachidonic acid from phospholipids |
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Authors: | G. K
saki, T. Nomura,J. Kambayashi |
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Affiliation: | G. Kōsaki, T. Nomura,J. Kambayashi |
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Abstract: | The inhibitory effect of proteinase inhibitors on platelet aggregation was investigated. The proteinase inhibitors tested were SBTI, leupeptin and FOY (a synthetic proteinase inhibitor). Also, synthetic substrates for serine proteinases (TLME, ATEE) were tested. They completely inhibited the secondary aggregation of platelets induced by ADP or epinephrine. They also completely inhibited the platelet aggregation induced by collagen or thrombin. The aggregation induced by arachidonic acid was completely inhibited by all the proteinase inhibitors and synthetic substrates. The aggregation induced by Ca ionophore A 23187 was completely inhibited by leupeptin, FOY, TLME or ATEE but not by SBTI. It is generally accepted that platelet prostaglandin metabolism plays an important role in platelet aggregation. As the first step to elucidate the possible mechanism of the inhibitory effect of the proteinase inhibitors, their effect on the release of arachidonic acid from platelet phospholipids was investigated. The release of arachidonic acid from 14C-arachidonate incorporated gel filtered platelets (14C-AA-GFP) by thrombin or A 23187 was directly measured in the presence or absence of a proteinase inhibitor or synthetic substrate, utilizing thin layer chromatography (TLC) and a scintillation counting. The release was almost completely blocked when the aggregation of 14C-AA-GFP by thrombin or A 23187 was completely inhibited by a proteinase inhibitor or a synthetic substrate. |
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Keywords: | platelet proteinase inhibitor arachidonic acid |
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