Inhibition by ibudilast of leukotriene D4-induced formation of inositol phosphates in guinea-pig lung
| Autor: | Susumu Etoh, Heitaroh Iwata, Mitsuo Ohashi, Akemichi Baba |
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| Rok vydání: | 1990 |
| Předmět: |
Male
medicine.medical_specialty GTP' G protein Pyridines Inositol Phosphates Vasodilator Agents Guinea Pigs Ibudilast Pharmacology Biology In Vitro Techniques Hippocampus chemistry.chemical_compound Calcium Chloride GTP-Binding Proteins Internal medicine medicine Animals Inositol Phosphatidylinositol Inositol phosphate Lung chemistry.chemical_classification Membranes Phospholipase C respiratory system Endocrinology Mechanism of action chemistry SRS-A Guanosine Triphosphate medicine.symptom medicine.drug Research Article |
| Zdroj: | British journal of pharmacology. 100(3) |
| ISSN: | 0007-1188 |
| Popis: | 1. The effects of a novel anti-asthmatic drug, 3-isobutyryl-2-isopropylpyrazolo [1,5-a]pyridine (ibudilast, KC-404) on leukotriene D4 (LTD4)-induced formation of inositol phosphates were studied in slices of guinea-pig lung and hippocampus. 2. In guinea-pig lung, ibudilast inhibited LTD4 (0.01-1 microM)-induced formation of inositol monophosphate (IP1) in a concentration-dependent manner (IC50 = 10 microM) without affecting LTD4 receptor binding. 3. Ibudilast (10 microM) inhibited histamine (0.1-1 mM)-induced formation of IP1 in guinea-pig lung slices but not in hippocampal slices. 4. Inhibition of agonist-induced formation of IP1 by ibudilast was non-competitive. 5. Ibudilast had no effect on either GTP- or calcium-stimulated phosphatidylinositol specific-phospholipase C activity of lung membranes. 6. These results suggest that ibudilast has no direct effect on LTD4 receptors, GTP binding proteins (G proteins) or phospholipase C, but inhibits inositol phosphate formation, possibly by interfering with the coupling between receptors and G proteins. |
| Databáze: | OpenAIRE |
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