Akira Ohtsu

Estradiol suppresses electrically-induced arterial thrombosis by increasing prostaglandin biosynthesizing activity of the aorta in rats

The anti-thrombotic effect of estradiol was studied using an electrically induced thrombus model in rats. Estradiol treatment significantly inhibited the thrombus formation induced by electric shock. In the meantime, a stimulation of prostacyclin biosynthesis by estradiol in aortas was found. This is the first report showing the correlation between the effects of the estradiol on the thrombus formation in an experimental model and on the prostacyclin production by aortas in the same animal system.

Effects of a novel fatty acid derivative [(7E)-8-(2-naphthyl)-5,6trans-5,6-methano-7-octenoic acid] on arachidonic acid metabolism in cultured cells

The effects of a novel synthetic fatty acid derivative (TEI-8005:(7E)-8-(2-naphthyl)-5,6-trans-5, 6-methano-7-octenoic acid) on arachidonic acid metabolism in some cultured cells were studied. The compound significantly stimulated prostaglandin (especially prostacyclin) biosynthesis in cultured vascular cells and gastric mucosal epithelial cells, and inhibited lipoxygenase product formation in n-butyrate-treated mastocytoma. In aortic smooth muscle cells in which cyclooxygenase activity was reduced, it strongly stimulated prostaglandin formation in young cells with reduced cyclooxygenase activity but had less effect in aged cells. These result indicated that TEI-8005 enhanced prostaglandin formation in cells with either normal or reduced cyclooxygenase activity.

Effects of a novel acylindole derivative on experimental thrombotic models, ulceration of the gastric mucosa and prostacyclin production in the aorta

Abstract 3-Benzoyl-N-β-ethoxyisopropyl-2-methylindole (TEI-4120) strongly inhibited arachidonic acid- and collagen-induced aggregation of platelets of several animal species (IC 50 : 3.3×10 −6 M − 3.1×10 −8 M). It also inhibited the second phase of ADP- or epinephrine-induced human platelet aggregation (IC 50 : 2.0×10 −6 M − 1.0×10 −5 M). TEI-4120 at oral doses of 1–30 mg/kg was effective on aggregation of platelets removed from animals. In several experimental thrombotic models, TEI-4120 at doses of 1–30 mg/kg (p.o.) inhibited thrombus formation. It was less ulcerogenic than typical nonsteroidal antiinflammatory drugs such as indomethacin and caused only slight gastric lesions at a dose of 400 mg/kg (p.o.). It was also only a weak inhibitor of prostacyclin biosynthesis in rat aorta in vivo, a dose of about 100 mg/kg being required to inhibit prostacyclin biosynthesis. These results show that TEI-4120 has strong anti-platelet activity and suggest that it should be a good anti-thrombotic drug with weak side effects.

Inhibition of prostaglandin synthesizing enzymes by haptoglobin and plasma of rat with inflammation

ラットの足蹠にcarrageenin, compound48/80あるいはadjvantを注射すると, 一定時間後の血漿にprostaglandin E2生合成の阻害作用およびhaptoglobin値の増加が認められた.一方, 部分精製したhaptoglobinはarachidonic acidを基質とするprostaglandin E2生合成を用量依存性に阻害した.ウシ精嚢microsomeの精製酵素を用いてその作用機作を検討したところ, haptoglobinが活性化因子のhemeと相互作用して阻害作用を示すことが明らかになった.しかし, prostaglandin E2生合成に対して阻害作用を示すhaptoglobin濃度 (ID50) は, 炎症ラット血漿では11μg/mlであるのに対して, 部分精製したhaptoglobinでは175μg/mlであり, 炎症ラット血漿の阻害作用をhaptoglobinのみで説明できないことが示唆された.