Effect of OKY-046, a selective thromboxane inhibitor, on prostaglandin production and function of pregnant rat uteri and platelets.
The effect of OKY-046 (ONO, Japan), a selective TX inhibitor, was studied for its effect on uterine and platelet activity. On day 21 of pregnancy, rats were injected with either 0, 1, or 5 mg/kg OKY-046 via the tail vein. One hour following injections, in vitro activity of uteri and platelets was assessed. A decrease (P less than .01) in uterine TXB2 production (measured by RIA) occurred with increasing OKY-046 dose (104 +/- 31 vs 44 +/- 6 vs 24 +/- 2 ng TXB2/g tissue/45 min). OKY-046 treatment had no effect on other prostanoids. Contractile activity was not affected by OKY-046. The amount of TXB2 produced in platelets from OKY-046 (5 mg/Kg) treated rats was 45.5% less than that from controls (P less than .001). Likewise, arachidonate-induced aggregation of platelets from OKY-046 treated rats was 46.1% less (P less than .05) than that of controls. In summary, in vivo administration of OKY-046 selectively reduced uterine TXB2 without altering other prostanoids, or affecting uterine contractions. In contrast, both platelet TXB2 production and platelet function (aggregation) was decreased.
Ghodgaonkar
R B
RB
Dubin
N H
NH
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000179:Acrylates / Q000494:pharmacology*; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D015237:Dinoprost; D015232:Dinoprostone; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D008689:Methacrylates / Q000494:pharmacology*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000096:biosynthesis; D011460:Prostaglandins F / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D013929:Thromboxane B2 / Q000096:biosynthesis; D013931:Thromboxanes / Q000037:antagonists & inhibitors*; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
D000179:Acrylates; D007093:Imidazoles; D008689:Methacrylates; D011453:Prostaglandins; D011458:Prostaglandins E; D011460:Prostaglandins F; D013931:Thromboxanes; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C029899:imidazole; D015237:Dinoprost; D015232:Dinoprostone; C034364:ozagrel