dinoprost and baicalein

Isoprostaglandin F(2alpha) type-III (formerly known as 8-iso-prostaglandin F(2alpha)) is produced in large quantities in vivo in clinical situations associated with oxidant stress such as atherosclerosis, hypercholesterolemia, and myocardial reperfusion. Isoprostaglandin F(2alpha) type-III may alter smooth muscle and platelet functions. The aim of this study was to evaluate the effects of isoprostaglandin F(2alpha) type-III on isolated human internal mammary arteries, and to characterise the signalling underlying mechanisms. In organ baths, concentration-dependent contractions of human internal mammary arteries were obtained in response to isoprostaglandin F(2alpha) type-III stimulation. The responses to isoprostaglandin F(2alpha) type-III were inhibited in a concentration-dependent manner by the thromboxane A(2) receptor antagonist, GR 32191 ([1R-[1 alpha(Z), 2beta,3beta,5 alpha(+)-7-[[1, 1'-biphenyl)-4-yl]methoxy]-3-hydroxy-2-(1-piperidinyl) cyclo pentyl]-4-4heptanoic acid], hydrochloride), 3x10(-9) to 3x10(-7) M). However, this effect was associated with a decreased maximal contraction. AH 6809 (6-isopropoxy-9-oxoxanthene-2-carboxylic acid, 10(-6) to 3x10(-5) M), an EP(1)-DP receptor antagonist had no effect on isoprostaglandin F(2alpha) type-III-induced contractions. The maximal responses to isoprostaglandin F(2alpha) type-III were significantly reduced in the presence of the cyclooxygenase inhibitor indomethacin (10(-5) M) (E(max): 147+/-20% vs. 213+/-19% in control group, P<0.05). Isoprostaglandin F(2alpha) type-III stimulated thromboxane B(2) release (5.7-fold increase) from human internal mammary arteries. Baicaleine, a non-specific lipoxygenase inhibitor, (10(-4) M) and AA 861 (2,3,5-trimethyl-6-(12-hydroxy-5, 10-dodecadiynyl)-1,4 benzoquinone), a 5-lipoxygenase inhibitor (10(-5) M) did not affect isoprostaglandin F(2alpha) type-III response. In conclusion, this study shows that (1) isoprostaglandin F(2alpha) type-III is a vasoconstrictor in human internal mammary arteries, with a potency equivalent to prostaglandin F(2alpha), (2) the contractions induced by isoprostaglandin F(2alpha) type-III are mediated by TP receptor but not EP(1)-DP-receptor activation, (3) thromboxane A(2) but not cysteinyl leukotrienes production is involved in the vascular effects of isoprostaglandin F(2alpha) type-III. Isoprostaglandin F(2alpha) type-III, produced at sites of free radical generation, may play an important role in internal mammary artery spasm in situatio

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adult; Aged; Benzoquinones; Biphenyl Compounds; Dinoprost; Dose-Response Relationship, Drug; F2-Isoprostanes; Female; Flavanones; Flavonoids; Heptanoic Acids; Humans; In Vitro Techniques; Leukotrienes; Lipoxygenase Inhibitors; Male; Mammary Arteries; Middle Aged; Prostaglandin Antagonists; Receptors, Prostaglandin E; Receptors, Prostaglandin E, EP1 Subtype; Receptors, Thromboxane; Thromboxane B2; Vasoconstriction; Vasoconstrictor Agents; Xanthenes; Xanthones

Effects of baicalein on release of slow reacting substance of anaphylaxis (SRS-A) or leukotriene (LT) from the sensitized guinea pig lung after antigen challenge and tonus of guinea pig tracheal muscles were studied. Baicalein inhibited release of SRS-A from sensitized guinea pig lung after antigen challenge. High-performance liquid chromatography (HPLC) analysis revealed that released SRS-A consisted to LTC4 and D4. Baicalein also reduced release of LTC4 and D4 from the sensitized lung after antigen challenge. Baicalein relaxed the isolated guinea pig tracheal smooth muscle contracted by LTD4, carbachol or histamine. However, this compound produced a contraction when the tracheal muscle was contracted by prostaglandin F2 alpha(PGF2 alpha). This contraction by baicalein was abolished by pretreatment with indomethacin, a cyclooxygenase inhibitor. Baicalein elicited a relaxation in the normal non-sensitized preparation but a contraction in the tissue isolated from actively sensitized guinea pig in 4 among 7 cases. Baicalein also produced a contraction in the trachea pretreated with phorbol dibutyrate and contracted by carbachol, which was eliminated after treatment with indomethacin. The results suggest that baicalein exerts action via, at least, two different mechanisms, the inhibition of releasing SRS-A (LTs) and direct relaxing effects on the trachea. Besides, baicalein seems to produce contraction under certain conditions, which may involve stimulation of the cyclooxygenase pathway.

Topics: Animals; Biological Assay; Chromatography, High Pressure Liquid; Cyclooxygenase Inhibitors; Dinoprost; Dose-Response Relationship, Drug; Enzyme Activation; Enzyme Inhibitors; Flavanones; Flavonoids; Guinea Pigs; Ileum; Indomethacin; Lung; Male; Muscle Contraction; Muscle, Smooth; Ovalbumin; Oxytocics; Protein Kinase C; SRS-A; Trachea

The role of endogenously produced arachidonic acid metabolites on glomerulonephritis was investigated using cultured rat mesangial cells. The cultured mesangial cells could produce prostaglandin (PG) E2 and F2 alpha and 12-hydroxyeicosatetraenoic acid (12-HETE). The treatment of the mesangial cells with indomethacin enhanced the cell growth stimulated by 10% fetal calf serum (FCS). This stimulatory effect was significantly attenuated by concomitant treatment with PGE2, but not with PGF2 alpha. To test whether the mechanism by which PGE2 inhibited the mesangial cell growth is related to in the increment of cyclic AMP (cAMP), we examined the effect of dibutyryl cAMP on mesangial cell growth. As expected, treatment with dibutyryl cAMP decreased the cell proliferation. Moreover treatment with KT-5720, a protein kinase A (PKA) inhibitor, stimulated the cell growth as well as indomethacin. These data strongly suggest that the inhibition of mesangial cell growth by PGE2 involves an activation of PKA. In contrast, treatment with baicalein, a specific inhibitor of 12-lipoxygenase, inhibited the mesangial cell growth. The up and down regulations by arachidonic acid metabolites were also observed in the growth induced by platelet-derived growth factor (PDGF). These results suggest that endogenously produced arachidonic acid metabolites are involved in the regulation of mesangial cell growth.

Topics: 1-Methyl-3-isobutylxanthine; 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Animals; Arachidonic Acid; Benzeneacetamides; Bucladesine; Carbazoles; Cell Division; Cells, Cultured; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Dinoprost; Dinoprostone; DNA Replication; Flavanones; Flavonoids; Glomerular Mesangium; Hydroxamic Acids; Hydroxyeicosatetraenoic Acids; Indoles; Indomethacin; Lipoxygenase Inhibitors; Male; Platelet-Derived Growth Factor; Pyrroles; Rats; Rats, Sprague-Dawley; Umbelliferones