The effect of tranylcypromine on levels of 6-keto-PGF(1α) and other prostaglandins in brain and mesentery of the mouse

Tranylcypromine (TCP), which can inhibit prostacyclin (PGI ₂) synthesis in vitro, has been shown to facilitate platelet aggregation in damaged cerebral arterioles of the mouse when given intraperitoneally (50 mg/kg) one hour before inducing aggregation. The same dose has no effect on platelet aggregation in damaged mesenteric arterioles. The present experiments used HPLC and GC/MS to analyze PG levels and show that 5 or 50 mg/kg TCP, given intraperitoneally one hour before sacrificing the mouse, moderately reduces the level of 6-keto-PGF(1α), the stable metabolite of PGI ₂, in incubated brain homogenates. This finding supports the hypothesis that TCP's enhancement of platelet aggregation in the brain was affected by a reduction in PGI ₂ levels. When 500 μg/ml TCP was added to the incubate of brain homogenate from mice given 50 mg/kg, PGE ₂ levels were reduced as well as the levels of 6-keto-PGF(1α). In incubated mesentery, the level of 6-keto-PGF(1α) was also reduced by treating mice with 50/kg TCP. The latter result failed to support the hypothesis that levels of mesenteric 6-keto-PGF(1α) would be unaltered by TCP in parallel with the inability of TCP to alter platelet aggregation in mesenteric arterioles. Thus our data fails to support an overall hypothesis relating TCP action on platelet aggregation to its inhibitory effect on PGI ₂ synthesis. At the same time the data do not rule out such a relationship for mouse brain.