thromboxane-b2 and dauricine

To observe the effect of phenolic alkaloids of Menispermum dauricum (PAMD) on thrombosis and platelet aggregation, and to explore its mechanism of action.. Thrombosis was observed with arteriovenous shunt thrombus model in rat; platelet aggregation was determined by Born's method; ultrastructure of platelet was observed by transmission electron microscope; TXB2 or 6-keto-PGF1alpha levels were assessed by radioimmunoassay; and NO was determined by colorimetric method.. PAMD dose-dependently inhibited experimental thrombus formation, platelet aggregation induced by ADP, AA and THR in vivo and ultrastructure changes stimulated by THR; PAMD increased the generation of 6-keto-PGF1alpha in thoracic aortae and NO level in plasma; and had no influence on TXB2 release (P > 0.05).. PAMD inhibited thrombosis and platelet aggregation, and its mechanism might be due to the increase of PGI2 and NO level.

Topics: 6-Ketoprostaglandin F1 alpha; Alkaloids; Animals; Aorta, Thoracic; Benzylisoquinolines; Blood Platelets; Dose-Response Relationship, Drug; Epoprostenol; Male; Menispermum; Nitric Oxide; Plants, Medicinal; Platelet Aggregation; Rabbits; Rats; Rats, Sprague-Dawley; Rhizome; Tetrahydroisoquinolines; Thrombosis; Thromboxane B2

The effects of dauricine (Dau), aniso amine (Ani), platelet activating factor (PAF), leukotriene C4 (LTC4) and leukotriene D4 (LTD4) on the production of TXB2 and 6-keto-PGF1 alpha (the stable metabolites of TXA2 and PGI2, respectively) in bovine anterior cerebral arterial smooth muscle cells were studied. The normal quantities of TXB2 and 6-keto-PGF1 alpha produced by bovine anterior cerebral arterial smooth muscle cells were 16 +/- 5 and 464 +/- 24 pg/10(5) cells, respectively, when measured by radioimmunoassay (RIA). The levels of TXB2 and 6-keto-PGF1 alpha in bovine anterior cerebral arterial smooth muscle cells decreased significantly when the cells were treated with Dau or Ani over 20 min. Both drugs inhibited the production of TXB2 and 6-keto-PGF1 alpha in dose (1-100 mumol/L) dependent manner. The bovine anterior cerebral arterial smooth muscle cells were stimulated markedly by LTC4 and LTD4 to produce TXB2 and 6-keto-PGF1 alpha on the same condition even at 0.01 mumol/L. When the cells were treated with PAF over 20 min, TXB2 increased significantly, but 6-keto-PGF1 alpha remained unchanged. If the cells were preincubated with Dau or Ani 20 min before PAF, LTC4 or LTD4 stimulation, the production of TXB2 and 6-keto-PGF1 alpha especially TXB2 were inhibited significantly compared with that of PAF, LTC4 or LTD4 group, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Alkaloids; Animals; Benzylisoquinolines; Cattle; Cells, Cultured; Cerebral Arteries; Isoquinolines; Muscle, Smooth, Vascular; Solanaceous Alkaloids; Tetrahydroisoquinolines; Thromboxane B2

The effects of dauricine (Dau), an isoquinoline alkaloid and anti-arrhythmic agent used in China recently, on the biosynthesis of metabolites of arachidonic acid in rat pleural neutrophils, comparing with dazoxiben, indomethacin and BW-755 c, were studied. The major products of metabolism by 5-lipoxygenase (5-LPO), measured by HPLC, were LTB4 and 5-HETE, whereas the major cyclooxygenase products measured by HPLC and RIA, were HHT and TXB2. The formation of all products by neutrophils was significantly depressed by Dau in a dose-dependent manner. The concentration of Dau required to obtain 50% inhibition (IC50) of formation of HHT, TXB2, LTB4 and 5-HETE was 25.3, 59.3, 31.8 and 59.5 mumol/L, respectively. These results indicate that the two major metabolic pathways of arachidonic acid in rat pleural neutrophils are inhibited by Dau.

Topics: Alkaloids; Animals; Arachidonic Acids; Benzylisoquinolines; Dose-Response Relationship, Drug; Fatty Acids, Unsaturated; Hydroxyeicosatetraenoic Acids; Isoquinolines; Leukotriene B4; Male; Neutrophils; Rats; Rats, Inbred Strains; Tetrahydroisoquinolines; Thromboxane B2

Dauricine (Dau), an isoquinoline alkaloid extracted from the roots of Menispermum dauricum D. C. and used as an antiarrhythmic agent in China recently, was shown to inhibit rat platelet aggregation induced by arachidonic acid (AA) and ADP, as well as human platelet aggregation induced by AA, ADP and adrenaline (Adr) in vitro in a dose-dependent manner. The concentration of Dau required for 50% inhibition (IC50) of rat platelet aggregation induced by AA and ADP was 26 and 37 mumol/L, respectively. For human platelet aggregation induced by AA, ADP and Adr the IC50 of Dau was found to be 39, 55 and 43 mumol/L, respectively. Dau inhibited the cyclooxygenase pathway metabolites of AA (TXB2 and HHT) in washed intact rat platelets. The production of TXB2 and HHT was reduced by 26% and 19%, respectively, when the Dau concentration was 50 mumol/L and by 46 and 45%, respectively, when the concentration of Dau was 100 mumol/L. The formation of 12-HETE was also inhibited at 100 mumol/L of Dau. The inhibitory effect of Dau on AA metabolism may be one of the mechanisms related to its inhibition of platelet aggregation.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Alkaloids; Animals; Arachidonic Acids; Benzylisoquinolines; Fatty Acids, Unsaturated; Hydroxyeicosatetraenoic Acids; Isoquinolines; Male; Platelet Aggregation; Platelet Aggregation Inhibitors; Rats; Rats, Inbred Strains; Tetrahydroisoquinolines; Thromboxane B2

Three groups of ten dogs underwent 80 minutes cardiopulmonary bypass. Two of the three groups were administered dauricine, as a new calcium channel blocker, and verapamil, as a generally recognized calcium channel blocker, respectively, from 15 minutes pre-bypass to the end of the bypass procedure (a period of 95 minutes). By means of radioimmunoassay plasma 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TxB2) as the stable metabolites of prostacyclin and thromboxane A2 were surveyed. During the aortic clamping the hemodynamic changes were recorded. The dauricine and verapamil groups showed markedly inhibited generation of excessive 6-keto-PGF1 and TxB2, a narrowed ratio of TxB2 to 6-keto-PGF1 alpha, as well as a reduced total systemic peripheral resistance within the perfusion period. These results suggest that dauricine and verapamil have a salutary effect in extracorporeal circulation. The possible mechanisms are discussed.

Topics: 6-Ketoprostaglandin F1 alpha; Alkaloids; Animals; Benzylisoquinolines; Calcium Channel Blockers; Cardiopulmonary Bypass; Dogs; Female; Heart Arrest, Induced; Isoquinolines; Male; Potassium; Tetrahydroisoquinolines; Thromboxane B2; Time Factors; Verapamil