Disease relevance of Piriprost

• Both meclofenamate (1 microM), a cyclooxygenase inhibitor, and U-60,257 (10 microM), a lipoxygenase inhibitor, attenuated the bone marrow-induced pulmonary hemodynamic response, whereas only U-60,257 attenuated the increases in lung wet weight and the capillary filtration coefficient [1].
• U-60,257 inhibits O3-induced bronchial hyperreactivity in the guinea pig [2].
• The effects of two specific 5-lipoxygenase inhibitors AA-863 and U-60,257 (piriprost) on the growth of two human glioma cell lines, U-343 MGa and U-251 MG were investigated [3].
• The IgE-mediated hypersensitivity to Ascaris antigen in reactor rhesus primates was used to assess the pharmacologic profile of U-60,257, a pyrrole analog of prostacyclin [4].

High impact information on Piriprost

• Walker 256 rat breast carcinoma cells (WS), with acquired resistance to nitrogen mustards (WR), and two human colon carcinoma cell lines, HT 29 and BE, were sensitized to chlorambucil when either ethacrynic acid or piriprost was administered at the same time as the alkylating agent [5].
• Ethacrynic acid and piriprost (6,9-deepoxy-6,9-(phenylimino)-delta 6,8-prostaglandin I1) have been shown to potentiate the cytotoxic activity of chlorambucil in rat and human tumor cell lines [5].
• Ethacrynic acid and piriprost as enhancers of cytotoxicity in drug resistant and sensitive cell lines [5].
• Lipophilic hydroxypyridinones inhibit 5-lipoxygenase at equivalent concentrations to the established inhibitor, piriprost, and show additional but minor anti-phospholipase A2 activity [6].
• When IL-3 is added in the presence of any of three lipoxygenase inhibitors tested (Piriprost, caffeic acid, nordihydroguiaretic acid) or FLAP inhibitor, MK-886, there is dose-dependent inhibition of the resumption of proliferation and of DNA synthesis [7].

Biological context of Piriprost

• This performed in presence of increasing concentration of the 5-lipoxygenase inhibitors AA-861 or U-60,257 caused a dose-dependent inhibition of the release of all LTs with an IC50 of approximately 10(-8) to 10(-7) M and 10(-6) M, respectively [8].
• U-60,257 had virtually no effect on oxygen radical production and degranulation, but chemotaxis was moderately suppressed [9].
• We therefore studied the effects of piriprost (U 60257), a putative leukotriene synthesis inhibitor, on thirteen fetal lambs at 137 to 140 days gestation [10].
• Inhibition of the presumably leukotriene-dependent component of antigen-induced bronchoconstriction in the guinea pig by piriprost (U-60,257) [11].
• Since leukotriene release might be associated with leukocyte activation in this model, seven additional dogs were pretreated by inhalation of 10 mg of the leukotriene inhibitor U-60,257 [12].

Anatomical context of Piriprost

• However, treatment of canine neutrophils with the 5-lipoxygenase inhibitor piriprost attenuated (p < 0.02) their contractile effect on vascular rings, suggesting that neutrophil generated 5-lipoxygenase products were probably responsible for smooth muscle contraction [13].
• Piriprost had similar inhibitory effects on the trachea, but not on lung parenchyma [14].
• Experiments on the mode of action of piriprost (U-60,257), an inhibitor of leukotriene formation in cloned mouse mast cells and in rat basophil leukemia cells [15].
• Our previous observation that piriprost is only a very weak inhibitor of the solubilized LTC synthase of rat basophil leukemia cells was extended to similar enzyme preparations derived from the mouse mast cells (IC50 1.5 mM) [15].
• Effect of 6,9-deepoxy-6,9-(phenylimino)-delta 6,8-prostaglandin 1(1) (U-60,257), an inhibitor of leukotriene synthesis, on human neutrophil function [16].

Associations of Piriprost with other chemical compounds

• On separate study days subjects inhaled either piriprost 1 mg or vehicle placebo, followed 15 minutes later by the PS25 allergen or exercise [17].
• Indomethacin decreased the inhibitory effect of piriprost on the trachea, but facilitated inhibition by this agent on the parenchyma [14].
• We studied the effects on ozone-induced airway hyperreactivity of U-60,257, a pyrroloprostacyclin shown to inhibit leukotriene C/D biosynthesis in vitro [2].
• The present study investigated the effects of piriprost (U-60,257B; an inhibitor of LT synthesis) and various LTs on alkaline phosphatase (ALP) activity of rat endometrial stromal cells in vitro [18].
• U-60,257 has no effect on the metabolism of arachidonic acid in nonstimulated human polymorphonuclear leukocytes [19].

Gene context of Piriprost

• Piriprost, a specific inhibitor of 5-lipoxygenase, inhibits proliferation of these cell lines up to 95% with 50% cell inhibition at approximately 3 x 10(-5) M [20].
• The results are consistent with the conclusion that piriprost acts as an inhibitor of the 5-lipoxygenase reaction and that its activity in intact cells is not likely to involve the inhibition of the LTC synthase [15].
• U-60,257 did not inhibit the cyclooxygenase of human polymorphonuclear leukocytes [21].
• On the other hand, U-60,257 inhibited glutathione S-transferase activity of rat basophil leukemia cells (ID50, 37 microM), suggesting that this compound may inhibit the last step in LTC biosynthesis [21].
• Piriprost behaves thus as a specific and apparently competitive antagonist of fMLP: this action does not seem to involve lipoxygenase inhibition and might be exerted at the level of the fMLP receptor or its associated mechanisms of transduction [22].

Analytical, diagnostic and therapeutic context of Piriprost

• Stability studies on piriprost and piriprost potassium using high-performance liquid chromatography [23].
• On the other hand, pretreatment with drugs which blocked the action (receptor antagonists FPL55712, L-648,051 and ICI 198,615) or formation (biosynthesis inhibitors: U-60,257 and MK886) of leukotrienes consistently resulted in clear-cut inhibition of the allergic constriction in bronchi from both asthmatic and non-asthmatic subjects [24].
• The only pulmonary effect prevented by Piriprost was the increase in surfactant content (disaturated phosphatidylcholine: DSPC) in broncho-alveolar lavage gluid (BAL) [25].
• A new selective inhibitor of leukotriene formation, piriprost (U-60,257), has been observed to decrease both neutrophil accumulation in the myocardium and infarct size following coronary ligation in experimental animals [26].
• This stimulated production of 5-HETE could be reversed by prior perfusion of the lung with the drug piriprost, an inhibitor of the 5-lipoxygenase cascade [27].

References