The effect of tranylcypromine on levels of 6-keto-PGF1 alpha and other prostaglandins in brain and mesentery of the mouse.
Tranylcypromine (TCP), which can inhibit prostacyclin (PGI2) 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-PGF1 alpha, the stable metabolite of PGI2, 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 PGI2 levels. When 500 micrograms/ml TCP was added to the incubate of brain homogenate from mice given 50 mg/kg, PGE2 levels were reduced as well as the levels of 6-keto-PGF1 alpha. In incubated mesentery, the level of 6-keto-PGF1 alpha was also reduced by treating mice with 50 mg/kg TCP. The latter result failed to support the hypothesis that levels of mesenteric 6-keto-PGF1 alpha 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 PGI2 synthesis. At the same time the data do not rule out such a relationship for mouse brain.
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D015237:Dinoprost; D015232:Dinoprostone; D008297:Male; D008643:Mesentery / Q000032:analysis*; D051379:Mice; D010974:Platelet Aggregation / Q000187:drug effects; D011458:Prostaglandins E / Q000032:analysis / Q000037:antagonists & inhibitors; D011460:Prostaglandins F / Q000032:analysis / Q000037:antagonists & inhibitors*; D014191:Tranylcypromine / Q000494:pharmacology*
D011458:Prostaglandins E; D011460:Prostaglandins F; D014191:Tranylcypromine; D015237:Dinoprost; D015232:Dinoprostone; C100006:prostaglandin F1