Phosphoramidon, an inhibitor of endothelin-converting enzyme, prevents indomethacin-induced gastric mucosal damage in rats
| Autor: | Mahmudul Hassan, Naomi Tanaka, Hisayuki Fukutomi, Katsutoshi Goto, Hiromasa Kashimura, Hiroshi Muto, Akira Nakahara, Kazuhiko Matsumaru |
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| Rok vydání: | 1998 |
| Předmět: |
Male
medicine.medical_specialty Indomethacin Stomach Diseases Endogeny Endothelin-Converting Enzymes General Biochemistry Genetics and Molecular Biology Pathogenesis chemistry.chemical_compound Internal medicine medicine Animals Aspartic Acid Endopeptidases Protease Inhibitors Protein Precursors Rats Wistar General Pharmacology Toxicology and Pharmaceutics Neprilysin chemistry.chemical_classification Metalloproteinase Endothelin-1 Endothelins Anti-Inflammatory Agents Non-Steroidal Phosphoramidon Glycopeptides Metalloendopeptidases General Medicine Thiorphan Rats Endocrinology Enzyme chemistry Gastric Mucosa Endothelin receptor |
| Zdroj: | Life Sciences. 62:PL79-PL84 |
| ISSN: | 0024-3205 |
| DOI: | 10.1016/s0024-3205(97)01165-x |
| Popis: | Endothelin-1 (ET-1) is produced from inactive precursor big ET-1 by endothelin-converting enzyme-1 (ECE-1), a membrane-bound metalloprotease, structurally similar to another metalloprotease, neutral endopeptidase 24.11 (NEP). Although both phosphoramidon and thiorphan are metalloprotease inhibitors, the ECE activity is inhibited by phosphoramidon but not by thiorphan, a specific inhibitor of NEP. Therefore, to investigate whether an ECE inhibitor can prevent indomethacin-induced gastric mucosal damage in rats, we compared the effects between the two metalloprotease inhibitors on both gastric mucosal integrity and the levels of ET-1 and big ET-1 in gastric tissue. Phosphoramidon significantly decreased ET-1 levels, causing a concomitant big ET-1 increase and dose-dependently attenuated indomethacin-induced gastric mucosal damage. By contrast, thiorphan neither changed the ratio of ET-1/big ET-1 nor attenuated the damage. In conclusion, the prevention of gastric mucosal damage by an ECE inhibitor indicates that endogenous ET-1 may play an important role in the pathogenesis of indomethacin-induced gastric mucosal damage. |
| Databáze: | OpenAIRE |
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