Importance of gastric acid in gastric ulcer formation in rabbits with antibody-induced prostaglandin deficiency. Possible mechanism for the inhibition of acid formation by the proton pump inhibitor AG-1749 in isolated canine parietal cells. Binding site of omeprazole in hog gastric H+,K(+)-ATPase. Rx drugs

Drugs online research references

Gastroenterology. 1992 Nov;103(5):1467-74.
Importance of gastric acid in gastric ulcer formation in rabbits with antibody-induced prostaglandin deficiency.

Lee M, Aldred K, Lee E, Prince MD, Feldman M.

Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas.

The role of gastric acid in the development of gastroduodenal ulcers in prostaglandin-deficient conditions is unclear. In the current study, the effect of the proton pump inhibitor omeprazole on the formation of gastric ulcers was examined in a previously validated rabbit model of antibody-induced prostaglandin deficiency. Intragastric administration of 20 mg/kg omeprazole every 12 hours caused a profound suppression of gastric acidity (i.e., pH above 5 continuously). This same dose of omeprazole significantly reduced gastric ulcer formation induced by passive immunization with 6-keto-prostaglandin F1 alpha antibodies. It is concluded from these observations that gastric acid plays a critical role in the formation of gastric ulcers in rabbits with antibody-induced prostaglandin deficiency.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1426865&dopt=Abstract

note: kwd match prilosec online literature

J Pharmacol Exp Ther. 1990 Mar;252(3):1289-95.
Possible mechanism for the inhibition of acid formation by the proton pump inhibitor AG-1749 in isolated canine parietal cells.

Nagaya H, Satoh H, Maki Y.

Research & Development Division, Takeda Chemical Industries, Ltd., Osaka, Japan.

We have reported previously that 2-[[[3-methyl-4-(2,2,2-trifluorethoxy)-2-pyridyl]methyl] sulfinil]- 1H-benzimidazole (AG-1749) inhibits (H+ + K+)-adenosine triphosphatase after being transformed into its cyclic sulfenamide form (AG-2000) or disulfide form (AG-1812) under acidic conditions. In this study, mechanisms related to the inhibition of acid formation by AG-1749 were investigated in isolated canine parietal cells. AG-1749 suppressed the acid formation stimulated by histamine, carbachol or dibutyryl cyclic AMP with IC50 values of approximately 0.09 microM: AG-1749 being twice as potent as omeprazole. The inhibitory effect of AG-1749 was antagonized by dithiothreitol (1 mM). 2-Cyclo-hexen-1-one (3 mM) decreased cytosolic glutathione to less than 10% of control value, and caused a 3-fold increase in the inhibitory effect of AG-1749. Glutathione, however, when added exogenously, did not affect the action of AG-1749. The inhibition was reversed by removing AG-1749 from the medium or by adding dithiothreitol (1 mM). The reversal of inhibition by these two procedures was hardly affected by puromycin (100 microM) or cycloheximide (300 microM) but significantly prevented by 2-cyclo-hexen-1-one (1 mM). Exogenously added AG-2000 (10 microM) or AG-1812 (5 microM), active forms of AG-1749, did not inhibit acid formation.(ABSTRACT TRUNCATED AT 250 WORDS)

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2156997&dopt=Abstract

note: kwd match prilosec online literature

Biochem Biophys Res Commun. 1990 Mar 16;167(2):754-60.
Binding site of omeprazole in hog gastric H+,K(+)-ATPase.

Morii M, Takata H, Takeguchi N.

Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.

Omeprazole transforms into an active compound in an acidic environment, which is able to modify a sulfhydryl group of gastric H+,K(+)-ATPase. Omeprazole was transformed into a strongly fluorescent molecule by UV-light irradiation (excitation wavelength = 290 nm, emission wavelength = 335 nm). The omeprazole-modified residue of hog H+,K(+)-ATPase was estimated by the fluorescence of the omeprazole moiety and limited tryptic digestion of the enzyme. Among the four main tryptic digested subfragments, omeprazole was bound to the 67, 42 and 32-kDa subfragments, but not to the 52-kDa subfragment. Taking the amino acid sequence of this ATPase into consideration, we propose that omeprazole specifically binds with Cys322 in hog H+,K(+)-ATPase (Cys321 in rat).

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2157414&dopt=Abstract

note: kwd match prilosec online literature

Herbs and Pharmaceuticals Online || Hair Million herbal formula for hair loss and hair growth || Antibiotics and prescription medications online literature ||