title: Diversion of prostaglandin endoperoxide metabolism by selective inhibition of thromboxane A2 biosynthesis in lung, spleen or platelets.
abstract: Infusion of arachidonic acid through the guinea pig lung or the cat spleen causes a release of thromboxane A2 and prostaglandins, as measured by bioassay. After incubation of human platelets with arachidonate similar metabolites are formed, as demonstrated chromatographically. Infusion of imidazole (50-75 microgram/ml) through the lung or spleen specifically inhibits thromboxane A2 production and diverts the pathway to the prostaglandins, mainly prostaglandin F2alpha. In human platelets imidazole causes a dose-dependent inhibition of thromboxane A2 formation (ID50 5.5 X 10(-4) M). This inhibition is accompanied by a dose-dependent increase in prostaglandin F2alpha. Since thromboxane A2 induces platelet aggregation and is a potent vasoconstrictor, diversion of pathways to prostaglandins with opposite or less potent action might be of relevance in the treatment of cardiovascular diseases.
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001345:Autoradiography; D001681:Biological Assay; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D002415:Cats; D002417:Cattle; D002855:Chromatography, Thin Layer; D003864:Depression, Chemical; D006168:Guinea Pigs; D006801:Humans; D006880:Hydroxy Acids / Q000096:biosynthesis* / Q000097:blood; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood; D011453:Prostaglandins / Q000378:metabolism*; D011714:Pyrans / Q000096:biosynthesis / Q000097:blood; D011817:Rabbits; D051381:Rats; D013154:Spleen / Q000187:drug effects / Q000378:metabolism*
chemical_list: D001095:Arachidonic Acids; D006880:Hydroxy Acids; D007093:Imidazoles; D011453:Prostaglandins; D011714:Pyrans; D011451:Prostaglandin-Endoperoxide Synthases