Comparison of the effects of inhibitors of cytochrome P-450-mediated reations on human platelet aggregation and arachidonic acid metabolism
| Autor: | Aalt Bast, Frederick J. Zijlstra, Peter C. Bragt, Michael J. Parnham |
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| Rok vydání: | 1981 |
| Předmět: |
Blood Platelets
Male Platelet Aggregation Cytochrome Thromboxane Biophysics Arachidonic Acids In Vitro Techniques Biochemistry chemistry.chemical_compound Cytochrome P-450 Enzyme System Malondialdehyde medicine Animals Cytochrome P-450 Enzyme Inhibitors Humans Molecular Biology Arachidonic Acid Metyrapone biology Proadifen Thromboxanes Ligand (biochemistry) Butanones Rats Thromboxane B2 Amphenone B chemistry Microsomes Liver biology.protein Arachidonic acid Thromboxane-A synthase medicine.drug |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - General Subjects. 677:165-173 |
| ISSN: | 0304-4165 |
| Popis: | Metyrapone and SKF-525A, together with amphenone B, a structural analogue of metyrapone, which are all inhibitors of cytochrome P-450-mediated reactiors, were shown to inhibit the arachidonic acid-induced aggregation of human platelets. Amphenone B, like metyrapone, exhibited a type II (ligand) binding spectrum with rat liver microsomal cytochrome P-450, in contrast to SKF 525A which is a type I (substrate) binding agent. Independently of their type of binding spectra and of their maximum spectral change, however, the affinity of the three compounds for rat liver cytochrome P-450 showed a close proportional correlation with their platelet aggregation inhibitory potency. All three compounds inhibited the formation of [1−14C]thromboxane B2 from [1−14C]arachidonic acid by human platelets aggregated with collagen. The effect of metyrapone on the remaining labelled products suggested that it is a selective thromboxane synthesis inhibitor, while amphenone B exhibited activity reminiscent of cyclo-oxygenase inhibitors. SKF 525A produced complex effects possibly attributable to cyclo-oxygenase inhibition and enhanced lipid peroxidation, since it also enhanced platelet malonaldehyde formation, which the other two compounds inhibited. These data provide further support for a role of cytochrome P-450 in thromboxane synthesis and platelet aggregation. |
| Databáze: | OpenAIRE |
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