thromboxane-a2 and ciprostene

thromboxane-a2 has been researched along with ciprostene* in 2 studies

Other Studies

2 other study(ies) available for thromboxane-a2 and ciprostene

ArticleYear
Activation of thromboxane and prostacyclin receptors elicits opposing effects on vascular smooth muscle cell growth and mitogen-activated protein kinase signaling cascades.
    Molecular pharmacology, 1995, Volume: 48, Issue:5

    Thromboxane A2 stimulation of smooth muscle cells contributes to the development of vascular lesions after percutaneous transluminal coronary angioplasty. In view of this, we examined the signaling pathways stimulated by a thromboxane receptor agonist, U-46619, in cultures of rat aortic smooth muscle cells. Treatment of rat aortic smooth muscle cells with U-46619 induced cellular hypertrophy ([14C]leucine incorporation) without stimulating mitogenesis ([3H]thymidine incorporation). Analysis of signaling pathways elicited by U-46619 revealed enhanced tyrosine phosphorylation and increased enzymatic activity of mitogen-activated protein (MAP) kinase (Erk2). U-46619 also activated signaling proteins upstream of p21-ras, inducing tyrosine phosphorylation on Shc and complex formation between Shc and growth factor receptor binding protein-2 (GRB2). Exposure of cells to a stable prostacyclin analogue, ciprostene calcium, attenuated U-46619-induced cellular hypertrophy and MAP kinase activity. Ciprostene treatment elevated cellular cAMP and inhibited U-46619-induced tyrosine phosphorylation on Shc and Shc/GRB2 complex formation. These results demonstrate that stimulation of thromboxane A2 and prostacyclin receptors have opposing effects on smooth muscle cell hypertrophy and the signaling pathways associated with this process. We conclude that inhibition of Shc/GRB2 complex formation and MAP kinase activity by ciprostene may contribute to its ability to limit restenosis injury.

    Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adaptor Proteins, Signal Transducing; Animals; Calcium-Calmodulin-Dependent Protein Kinases; Cell Division; Cells, Cultured; Cyclic AMP; Enzyme Activation; Epoprostenol; GRB2 Adaptor Protein; Muscle, Smooth, Vascular; Prostaglandin Endoperoxides, Synthetic; Proteins; Rats; Receptors, Epoprostenol; Receptors, Prostaglandin; Receptors, Thromboxane; Thromboxane A2; Thymidine

1995
A pharmacological analysis of the pathophysiological mechanisms of posttraumatic spinal cord ischemia.
    Journal of neurosurgery, 1986, Volume: 64, Issue:6

    A pharmacological analysis was carried out to determine the possible role of aberrant calcium fluxes, vasoactive arachidonic acid metabolites, and microvascular lipid peroxidation in the development of posttraumatic spinal cord white matter ischemia. Pentobarbital-anesthetized cats were treated intravenously 30 minutes before a 500-gm-cm contusion injury to the lumbar spinal cord with one of the following test drugs: the Ca++ channel antagonists verapamil, diltiazem, or nifedipine; the cyclo-oxygenase inhibitors ibuprofen or meclofenamate; the thromboxane A2 (TXA2) synthetase inhibitor furegrelate sodium; or the stable epoprostenol (prostacyclin, or PGI2) analogue ciprostene calcium alone or in combination with furegrelate sodium. Another group of animals was pretreated for 5 days before spinal injury with a combination of the antioxidants vitamin E and selenium in high doses. The hydrogen clearance technique was used to make repeated measurements of spinal cord blood flow (SCBF) in the dorsolateral funiculus of the injured segment before and for 4 hours after injury. In 11 untreated uninjured cats, the mean preinjury SCBF was 12.7 +/- 1.5 ml/100 gm/min. Following contusion, there was a progressive decline in SCBF to 6.8 +/- 0.4 ml/100 gm/min, or 53.5% of the preinjury level at 4 hours. In comparison, the Ca++ antagonists diltiazem and nifedipine (but not verapamil) prevented a significant posttraumatic decrease in SCBF. Similarly, both cyclo-oxygenase inhibitors (ibuprofen and meclofenamate) maintained SCBF within normal limits (10 ml/100 gm/min or greater). However, neither TXA2 synthetase inhibition nor the stable PGI2 analogue alone had a significant effect in preventing ischemia, whereas a combination of the two agents did serve to support SCBF. The most impressive preservation of posttraumatic SCBF, however, was observed in the antioxidant-treated animals. Based upon these results, a hypothesis is presented concerning the pathogenesis of posttraumatic central nervous system ischemia which integrates an injury-induced rise in intracellular Ca++, the increased synthesis of vasoactive prostanoids (such as prostaglandin F2 alpha and TXA2), and progressive microvascular lipid peroxidation.

    Topics: Animals; Benzofurans; Calcium Channel Blockers; Cats; Cyclooxygenase Inhibitors; Diltiazem; Dinoprost; Epoprostenol; Female; Ibuprofen; Ischemia; Male; Meclofenamic Acid; Nifedipine; Prostaglandin Antagonists; Prostaglandins F; Spinal Cord; Thromboxane A2; Verapamil; Vitamin E

1986