BIOMAT Database Logo BIOMAT Database Logo

Nitrovasodilators inhibit thrombin-induced platelet-activating factor synthesis in human endothelial cells. 1992

R Heller, and F Bussolino, and D Ghigo, and G Garbarino, and G Pescarmona, and U Till, and A Bosia
Department of Pathological Biochemistry, Medical Academy, Erfurt, Federal Republic of Germany.

In response to inflammatory agents such as thrombin, cultured endothelial cells produce platelet-activating factor (PAF), which has been linked with most inflammatory and immune processes, and is a potent coronary constrictor. Sodium nitroprusside (SNP) and SIN-1 (3-morpholinosydnonimine), which spontaneously release the free radical nitric oxide (NO), cause direct relaxation of blood vessels and inhibition of platelet aggregation by activating soluble guanylate cyclase. In the present study we report that in human umbilical vein endothelial cells (HUVEC) these compounds stimulate the production of cGMP and inhibit thrombin-induced PAF synthesis in a concentration-dependent manner. 8-bromo-cGMP, a permeant non-hydrolysable analogue of cGMP, mimics the inhibitory effect of NO-generating vasodilators. PAF synthesis requires phospholipase A2-mediated hydrolysis of membrane precursors to lyso-PAF, which is in turn converted into PAF by an acetyltransferase. The thrombin-elicited activation of both enzymes is inhibited in a dose-dependent way in HUVEC pretreated with SNP and SIN-1. The inhibitory effect of SNP and SIN-1 on the thrombin-mediated PAF synthesis suggests a new mechanism of action whereby the endogenous NO can affect vascular tone and endothelium-dependent intercellular adhesion. Moreover, PAF production in endothelial cells appears to be an important target for the pharmacological action of nitrovasodilators.

UI MeSH Term Description Entries
D008981 Molsidomine A morpholinyl sydnone imine ethyl ester, having a nitrogen in place of the keto oxygen. It acts as NITRIC OXIDE DONORS and is a vasodilator that has been used in ANGINA PECTORIS. Morsydomine,Corpea,Corvaton,Duracoron,Fali-Cor,Korvatone,MTW-Molsidomin,Molsi 1A Pharma,Molsi-AZU,Molsi-Puren,Molsibeta,Molsicor,Molsidain,Molsidomin,Molsidomin Heumann,Molsidomin Stada,Molsidomin Von Ct,Molsidomin-Ratiopharm,Molsihexal,Molsiket,SIN-10,Sydnopharm,Fali Cor,Heumann, Molsidomin,MTW Molsidomin,Molsi AZU,Molsi Puren,Molsidomin Ratiopharm,SIN 10,SIN10,Von Ct, Molsidomin
D009599 Nitroprusside A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins. Nitroferricyanide,Sodium Nitroprusside,Cyanonitrosylferrate,Ketostix,Naniprus,Nipride,Nipruton,Nitriate,Nitropress,Nitroprussiat Fides,Nitroprusside, Disodium Salt,Nitroprusside, Disodium Salt, Dihydrate,Disodium Salt Nitroprusside,Nitroprusside, Sodium
D010972 Platelet Activating Factor A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION. AGEPC,Acetyl Glyceryl Ether Phosphorylcholine,PAF-Acether,Phosphorylcholine, Acetyl Glyceryl Ether,1-Alkyl-2-acetyl-sn-glycerophosphocholine,Platelet Aggregating Factor,Platelet Aggregation Enhancing Factor,Platelet-Activating Substance,Thrombocyte Aggregating Activity,1 Alkyl 2 acetyl sn glycerophosphocholine,Aggregating Factor, Platelet,Factor, Platelet Activating,PAF Acether,Platelet Activating Substance
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004730 Endothelium, Vascular Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components. Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D006152 Cyclic GMP Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed) Guanosine Cyclic 3',5'-Monophosphate,Guanosine Cyclic 3,5 Monophosphate,Guanosine Cyclic Monophosphate,Guanosine Cyclic-3',5'-Monophosphate,3',5'-Monophosphate, Guanosine Cyclic,Cyclic 3',5'-Monophosphate, Guanosine,Cyclic Monophosphate, Guanosine,Cyclic-3',5'-Monophosphate, Guanosine,GMP, Cyclic,Guanosine Cyclic 3',5' Monophosphate,Monophosphate, Guanosine Cyclic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000123 Acetyltransferases Enzymes catalyzing the transfer of an acetyl group, usually from acetyl coenzyme A, to another compound. EC 2.3.1. Acetyltransferase
D013917 Thrombin An enzyme formed from PROTHROMBIN that converts FIBRINOGEN to FIBRIN. Thrombase,Thrombin JMI,Thrombin-JMI,Thrombinar,Thrombostat,alpha-Thrombin,beta,gamma-Thrombin,beta-Thrombin,gamma-Thrombin,JMI, Thrombin

Related Publications

R Heller, and F Bussolino, and D Ghigo, and G Garbarino, and G Pescarmona, and U Till, and A Bosia
Platelet activating factor acether is involved in thrombin-induced synthesis of prostacyclin by human endothelial cells.
January 1987, Advances in prostaglandin, thromboxane, and leukotriene research,
R Heller, and F Bussolino, and D Ghigo, and G Garbarino, and G Pescarmona, and U Till, and A Bosia
Nitrovasodilators inhibit platelet-derived growth factor-induced proliferation and migration of activated human hepatic stellate cells.
August 2000, Gastroenterology,
R Heller, and F Bussolino, and D Ghigo, and G Garbarino, and G Pescarmona, and U Till, and A Bosia
Xanthines inhibit human platelet aggregation induced by platelet-activating factor.
August 1992, Clinical and experimental pharmacology & physiology,
R Heller, and F Bussolino, and D Ghigo, and G Garbarino, and G Pescarmona, and U Till, and A Bosia
Nitrovasodilators and cGMP inhibit human platelet activation.
September 1991, Cardioscience,
R Heller, and F Bussolino, and D Ghigo, and G Garbarino, and G Pescarmona, and U Till, and A Bosia
Activation of the acetyl-coenzyme A:lysoplatelet-activating factor acetyltransferase regulates platelet-activating factor synthesis in human endothelial cells.
November 1992, The Journal of biological chemistry,
R Heller, and F Bussolino, and D Ghigo, and G Garbarino, and G Pescarmona, and U Till, and A Bosia
Synthesis and release of platelet-activating factor and eicosanoids in human endothelial cells induced by different agonists.
March 1993, Agents and actions,
R Heller, and F Bussolino, and D Ghigo, and G Garbarino, and G Pescarmona, and U Till, and A Bosia
Stress-induced platelet-activating factor synthesis in human neutrophils.
April 2005, Biochimica et biophysica acta,
R Heller, and F Bussolino, and D Ghigo, and G Garbarino, and G Pescarmona, and U Till, and A Bosia
Regulation of PAF-acether (platelet-activating factor) biosynthesis in cultured human vascular endothelial cells stimulated with thrombin.
October 1987, Biochimica et biophysica acta,
R Heller, and F Bussolino, and D Ghigo, and G Garbarino, and G Pescarmona, and U Till, and A Bosia
Inhibition of platelet-activating factor (PAF) acetylhydrolase by methyl arachidonyl fluorophosphonate potentiates PAF synthesis in thrombin-stimulated human coronary artery endothelial cells.
December 2003, The Journal of pharmacology and experimental therapeutics,
R Heller, and F Bussolino, and D Ghigo, and G Garbarino, and G Pescarmona, and U Till, and A Bosia
Regulation of platelet-activating factor (PAF) synthesis and PAF-mediated neutrophil adhesion to endothelial cells activated by thrombin.
January 1992, Seminars in thrombosis and hemostasis,
Copied contents to your clipboard!