Indomethacin activates carbonic anhydrase and antagonizes the effect of the specific carbonic anhydrase inhibitor acetazolamide, by a direct mechanism of action
| Autor: | M Ifrim, G Domuta, M Coltau, A Hecht, Ioan Puscas, M Baican, T Maghiar |
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| Rok vydání: | 2009 |
| Předmět: |
Pharmacology
medicine.medical_specialty biology Chemistry medicine.drug_class Endocrinology Mechanism of action Indometacin In vivo Enzyme inhibitor Internal medicine Carbonic anhydrase medicine biology.protein Gastric acid Pharmacology (medical) Carbonic anhydrase inhibitor medicine.symptom Acetazolamide medicine.drug |
| Zdroj: | Int. Journal of Clinical Pharmacology and Therapeutics. |
| ISSN: | 0946-1965 |
| Popis: | Objectives In this paper we investigated the effect of indomethacin, acetazolamide and their combination in vitro and in vivo on carbonic anhydrase (CA) isozymes. Method In vitro experiments followed the effect of the two substances at concentrations between 10(-8)-10(-4) M on purified human red cell CA I and II as well as on human gastric mucosa CA IV using dose-response relationships. Kinetic studies were also performed. The effects of single and combined administration of indomethacin and acetazolamide on red cell CA and on gastric acid secretion were studied in vivo. Results Indomethacin, in vitro and in vivo. induces an increase in erythorcyte CA I and CA II activity. Acetazolamide, a specific inhibitor of CA, reduces the activity of CA I and CA II from red cells. Indomethacin completely antagonizes CA activity, i.e. abolishes the inhibitory effect of acetazolamide on CA. In humans, an increase or decrease in erythrocyte CA II activity is correlated with an increase or decrease in gastric acid secretion. Conclusions Our results show that indomethacin, a known cyclooxygenase (COX) inhibitor, is also an activator of CA. Our data also prove that indomethacin is not only an activator of CA but also antagonizes the effect of acetazolamide, a specific inhibitor of this enzyme. In view of the role of CA in acid-base balance as well as the fact that an increase or decrease in its activity is accompanied by an increase or decrease in intra- and extracellular pH, our results suggest that: firstly, CA activation induced by indomethacin might cause changes in COX activity; secondly, PGs are synthetized as a consequence of the changes in COX activity, a hypothesis that requires further study. |
| Databáze: | OpenAIRE |
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