Detail of "98299-61-7"

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Effects of a thromboxane synthetase inhibitor and a thromboxane antagonist on release and activity of thromboxane A2 and prostacyclin in vitro

Effects of a thromboxane synthetase inhibitor and a thromboxane antagonist on release and activity of thromboxane A2 and prostacyclin in vitro. O'Keefe, Eugene H.; Liu, Edward C. K.; Greenberg, Roland; Ogletree, Martin L. (Dep. Pharmacol., Squibb Inst. Med. Res., Princeton, NJ 08540, USA). Prostaglandins, 29(5), 785-97 (English) 1985. CODEN: PRGLBA. ISSN: 0090-6980. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) The TXA2 synthetase inhibitor, dazoxiben [78218-09-4], and the TXA2 antagonist, ±SQ 29,548 [98299-61-7], were examd. for effects on release and vasoactivity of TXA2 [57576-52-0] and PGI2 [35121-78-9]. Isolated perfused guinea pig lungs were used as the enzyme source from which TXA2 and PGI2 were released in response to injections of arachidonic acid [506-32-1] or bradykinin [58-82-2]. Both dazoxiben and ±SQ 29,548 inhibited contraction of the superfused rat aorta and bovine coronary artery after arachidonic acid injection through the lung. ±SQ 29,548 abolished contractions of the rat aorta, but aorta-contracting activity persisted during dazoxiben treatment. Dazoxiben inhibited arachidonate-induced release of TxA2 (immunoreactive TXB2 [54397-85-2]) into the superfusate, but TXA2 release was potentiated by ±SQ 29,548. Thus, in the presence of enhanced TXA2 concns., ±SQ 29,548 effectively antagonized the vasospastic effect of TXA2. Dazoxiben diverted a greater amt. of arachidonic acid into PGI2 synthesis (immunoreactive 6-keto-PGF1a [58962-34-8]), changing original coronary vasoconstriction into relaxation. ±SQ 29,548 did not modify lung PGI2 synthesis. Moreover, with ±SQ 29,548, the absence of TXA2-mediated coronary contraction unmasked active relaxation of the superfused bovine coronary artery, coincident with thromboxane and PGI2 release. Dazoxiben consistenly inhibited TXA2 synthesis and enhanced PGI2 synthesis. ±SQ 29,548 augmented TXB2 release in response to arachidonate, but not bradykinin, and did not alter 6-keto-PGF1a release in response to either arachidonate or bradykinin. In terms of vasoactivity measured in vitro, ±SQ 29,548 and dazoxiben produced similar anti-vasospastic effects, although this was accomplished by completely different mechanisms.