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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Windischhofer, W. Fauler, G. Köfeler, H. C. Leis, H. J. |
| Description | Author Affiliation: Köfeler HC ( Department of Biochemical Analysis and Mass Spectrometry, Pediatric Hospital, Graz, Austria. harald.koefeler@kfunigraz.ac.a) |
| Abstract | 1. The present study was carried out to clarify the effect of the imidazole antimycotics econazole, bifonazole and clotrimazole on prostanoid biosynthesis. Osteoblast-like MC3T3-E1 cells stimulated by endothelin-1, melittin, ionomycin or arachidonic acid showed diminished prostaglandin E(2) (PGE(2)) production upon pretreatment with econazole. Following pretreatment with bifonazole, stimulation with ionomycin or arachidonic acid also resulted in decreased PGE(2) formation. Clotrimazole inhibited ionomycin but not arachidonic acid stimulated PGE(2) synthesis in MC3T3-E1 cells. 2. The results observed in osteoblast-like UMR-106 cells pretreated with econazole, bifonazole or clotrimazole and stimulated by arachidonic acid were similar with the exception of clotrimazole which was a more effective inhibitor of PGE(2) biosynthesis than in MC3T3-E1 cells. 3. Upon treatment with arachidonic acid thromboxane B(2) (TXB(2)) production in human platelets was abolished completely at concentrations of the three imidazole antimycotics higher than 5 microM (IC(50)<1 microM). 4. These data were confirmed by a direct assay using purified ram seminal vesicle prostaglandin H(2) synthase-1 (PGHS-1), which clearly showed inhibitory properties of econazole (IC(50) 4.7+/-2.3 microM), bifonazole (IC(50) 9.4+/-0.8 microM) and clotrimazole (IC(50) 4.4+/-0.6 microM). 5. Summarizing, these results indicate an inhibitory effect of econazole, bifonazole and clotrimazole on PGHS-1, varying in its potency dependent on the cell system used. In addition TXB(2) formation is affected at doses even lower than those needed to suppress PGE(2) biosynthesis. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 6 |
| Volume Number | 130 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2000-07-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Cytochrome P-450 Enzyme Inhibitors Enzyme Inhibitors Pharmacology Prostaglandins Biosynthesis Animals Blood Platelets Drug Effects Metabolism Cell Line Clotrimazole Cyclooxygenase 1 Dinoprostone Dose-Response Relationship, Drug Econazole Imidazoles Ionomycin Isoenzymes Membrane Proteins Prostaglandin-Endoperoxide Synthases Thromboxane B2 Tumor Cells, Cultured Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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