Effects of Omeprazole, Famotidine, and Ranitidine on the Enzyme Activities of Carbonic Anhydrase from Bovine Stomach in Vitro and Rat Erythrocytes in Vivo

Abstract

Carbonic anhydrase (carbonate hydrolyase, E.C. 4.2.1.1) isozymes are a family of zinc metalloenzymes that catalyze the interconversion of CO 2 and HCO 3 .Ϫ1,2) The enzyme is abundantly present in mammalian red blood cells and to a lesser extent in different types of tissues and secretory organs. 3,4) In addition, carbonic anhydrase have been obtained and characterized from plant, yeast and bacteria. [4][5][6][7][8][9][10] The important roles of the enzyme in various cell types have been extensively reviewed. 4,5,10) Human and most mammalian red blood cell carbonic anhydrases are known to comprise two isozymes, I and II, however, ruminants and cats have only one isozyme II. 4)Carbonic anhydrases facilitate the one-for-one electroneutral exchange of Cl Ϫ for HCO 3 Ϫ and thereby contribute to pH regulation, CO 2 metabolism, volume regulation, and maintenance of Cl Ϫ and HCO 3 Ϫ levels. 11) In our stomach lining the play a role in secreting acid, while the same enzymes help to make pancreatic juices alkaline and our saliva neutral. Thus, carbonic anhydrase isozymes perform different functions at their specific locations, and their absence or malfunction can lead to diseased states, ranging from the loss of acid production to stomach failure. 12,13) Therefore, we examined the effects of omeprazole, famotidine, and ranitidine on stomach CA and erythrocyte CA, and compared the results for the 3 drugs with each other.It has been reported that the activity levels of CA isoenzymes in human erythrocytes vary considerably under certain pathological and physiological conditions. Changes in CA activity have been associated with metabolic diseases such as diabetes mellitus and hypertension.14,15) It has been reported that the inhibition of CA was found to impair proton secretion into the proximal tubule lumen and thereby decreased bicarbonate reabsorption. At the same time, inhibition of CA was also found to decrease the rate of acidification of urine, producing alkaline urine and eventually metabolic acidosis. 16) Omeprazole is a specific inhibitor of the H ϩ , K ϩ -ATPase or 'proton pump' in parietal cells. This enzyme is responsible for the final step in the process of acid secretion; omeprazole blocks acid secretion in response to all stimuli. It has also been shown to be highly effective in healing ulcers which have failed to respond to H 2 -receptor antagonists, and has been extremely valuable in treating patients with Zollinger-Ellison syndrome.17) Famotidine and ranitidine are H 2 blockers. They are available in prescription strength and over the counter. These drugs provide short-term relief, but over doses H 2 blockers. 18)In the present study, the in vitro effects of omeprazole on CA isoenzymes purified from bovine stomach and the in vivo effects on the CA enzyme from rat erythrocytes were investigated. Furthermore, in vitro and in vivo studies were performed with famotidine and ranitidine, which are used as H 2 blockers. Using the I 50 values obtained (causing 50% inhibition of enzyme activity), clinically, undesir...

In vivo and in vitro protective effects of omeprazole against neuropathic pain

“…Several other drugs like minocycline 16 and atorvastatin 3 are reported to attenuate the CCI-induced neuropathic pain through anti-inflammatory and antioxidant actions. Omeprazole is previously reported as an anti-inflammatory 13 17 , antioxidant 18 , carbonic anhydrase and cytokine release inhibitor 8 19 , and neuroprotective agent 14 . Recently, there is an increased interest in the repositioning of the proton pump inhibitors as anticancer agents through targeting the thioesterase domain of the fatty acid synthase 20 .…”

“…Omeprazole is a proton pump inhibitor that is widely used in the treatment of peptic ulcer 7 . In vitro and and in vivo evaluations have proved omeprazole have carbonic anhydrase inhibitory 8 , anti-inflammatory 9 and antioxidant 10 activities. Omeprazole following in vitro co-incubation with isolated human neutrophils showed to reduce hemotaxis and oxidative radical production induced by bacterial chemotactic tetrapeptide, N-formyl-Met-Leu-Phe (fMLP) 11 .…”

Famotidine, an Antiulcer Agent, Strongly Inhibits Helicobacter pylori and Human Carbonic Anhydrases

“…The third generation histamine H 2 receptor antagonists such as cimetidine, ranitidine, and famotidine (Figure ) are widely used for the treatment of duodenal and gastric ulcers, gastroesophageal reflux disease, and pathological hypersecretory conditions such as Zollinger–Ellison syndrome. − Famotidine incorporates a sulfamide moiety, a bioisostere of the sulfonamide group, a well-known zinc binding group present in carbonic anhydrase (CA, EC 4.2.1.1) inhibitors (CAIs) . However, the effects of famotidine on these zinc metallo-enzymes was scarcely investigated until now . CAs are ubiquitous metallo-enzymes that catalyze the reversible hydration of carbon dioxide to bicarbonate and protons. , In humans, 15 different α-isoforms are present, with a very different subcellular localization and tissue distribution .…”

Effect of Some Drugs on Sheep Liver Carbonic Anhydrase I and Ii

“…CA I and II have been purified many times from different organisms and the effects of various chemicals, pesticides and drugs on its activity have been investigated (Beydemir, 2000;Demir, 2004;Ottlecz, 1999;.…”

“…Inhibitor of carbonic anhydrase are very important for different diseases such as antiglaucoma, diuretics, antiepileptics, in the management of mountain sickness, gastric and duodenal ulcers, neurological disorders or osteoporosis (Supuran, 2000). CA I and II have been purified many times from different organisms and the effects of various chemicals, pesticides and drugs on its activity have been investigated (Beydemir, 2000;Demir, 2004;Ottlecz, 1999;.…”