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Titolo:
Indomethacin activates carbonic anhydrase and antagonizes the effect of the specific carbonic anhydrase inhibitor acetazolamide, by a direct mechanism of action
Autore:
Puscas, I; Ifrim, M; Maghiar, T; Coltau, M; Domuta, G; Baican, M; Hecht, A;
Indirizzi:
Romanian Med Acad Sci, Ctr Res & Med Assistance, Simleu Silvaniei 4775, Romania Romanian Med Acad Sci Simleu Silvaniei Romania 4775 vaniei 4775, Romania Univ Med Oradea, Simleu Silvaniei, Romania Univ Med Oradea Simleu Silvaniei Romania dea, Simleu Silvaniei, Romania Med Care Unit, New York, NY USA Med Care Unit New York NY USAMed Care Unit, New York, NY USA Klin Wilkenberg, Wilkenberg, Germany Klin Wilkenberg Wilkenberg GermanyKlin Wilkenberg, Wilkenberg, Germany
Titolo Testata:
INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS
fascicolo: 6, volume: 39, anno: 2001,
pagine: 265 - 270
SICI:
0946-1965(200106)39:6<265:IACAAA>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PROSTAGLANDINS; INCREASE; RAT;
Keywords:
carbonic anhydrase isozymes; indomethacin; acetazolamide; gastric acid secretion;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Puscas, I Romanian Med Acad Sci, Ctr Res & Med Assistance, 37 Dunarii St, Simleu Silvaniei 4775, Romania Romanian Med Acad Sci 37 Dunarii St Simleu Silvaniei Romania 4775
Citazione:
I. Puscas et al., "Indomethacin activates carbonic anhydrase and antagonizes the effect of the specific carbonic anhydrase inhibitor acetazolamide, by a direct mechanism of action", INT J CL PH, 39(6), 2001, pp. 265-270

Abstract

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 M-4 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 cellCA 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 IIactivity. Acetazolamide, aspecific 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 C-A. 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 alsoan activator of CA. Our data also prove that indomethacin is not only an activator of CA but also antagonizes the effect of acetazolamide, a specificinhibitor 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.

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Documento generato il 02/04/20 alle ore 00:28:19