Puscas I, Coltau M, Pasca R
Center for Medical Research and Assistance, Simleu Silvaniei, Salaj, Romania.
J Pharmacol Exp Ther. 1996 Jun;277(3):1464-6.
Previous studies by this research team proved that vasodilating prostaglandins (PGs) E1, E2 and I2 inhibit carbonic anhydrase (CA) in vitro and in vivo, which suggested involvement of CA in gastric acid secretion inhibition and the increase of gastric mucosa blood flow produced by this group of PGs. Relying on these findings, as well as on our clinical observations, we studied in vitro and in vivo the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on CA I and CA II. We also followed in vitro the effects on these isozymes of NSAIDs associated to histamine, Ca, PGE2 and acetazolamide. The results show that the NSAIDs used here, which reduce the activity of cyclooxygenase and PG production, activated CA I and CA II in a dose-dependent manner by a mechanism of the noncompetitive type. Histamine and Ca added to NSAIDs amplified the activating effect of the latter on CA II. Association of PGE2 or acetazolamide to NSAIDs reduced NSAID-induced activation of CA I and CA II. Indomethacin abolished the inhibitory effect of acetazolamide on CA I and CA II. Our data imply that between CA and cyclooxygenase there is an inverse relationship, CA activation being accompanied by reduction of cyclooxygenase activity, a reduction achieved by the pH modifications induced by CA activation. In this way, cyclooxygenase, inhibition occurs "via CA," with the pH variations it brings about.
该研究团队之前的研究证明，血管舒张性前列腺素（PGs）E1、E2和I2在体外和体内均能抑制碳酸酐酶（CA），这表明CA参与了胃酸分泌的抑制以及该组PGs引起的胃黏膜血流增加。基于这些发现以及我们的临床观察，我们在体外和体内研究了非甾体抗炎药（NSAIDs）对CA I和CA II的影响。我们还在体外观察了与组胺、钙、PGE2和乙酰唑胺相关的NSAIDs对这些同工酶的影响。结果表明，这里使用的NSAIDs可降低环氧化酶活性和PG生成，通过非竞争性机制以剂量依赖方式激活CA I和CA II。添加到NSAIDs中的组胺和钙增强了后者对CA II的激活作用。PGE2或乙酰唑胺与NSAIDs联合使用可降低NSAIDs诱导的CA I和CA II激活。吲哚美辛消除了乙酰唑胺对CA I和CA II的抑制作用。我们的数据表明，CA与环氧化酶之间存在负相关关系，CA激活伴随着环氧化酶活性降低，这种降低是由CA激活诱导的pH变化实现的。通过这种方式，环氧化酶的抑制是“通过CA”发生的，并伴随着其带来的pH变化。
