title: Effects of the enantiomers of lansoprazole (AG-1749) on (H+ + K+)-ATPase activity in canine gastric microsomes and acid formation in isolated canine parietal cells.
abstract: The effects of the enantiomers of 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]-sulfinyl ]- 1H-benzimidazole (lansoprazole, AG-1749) on acid formation in isolated canine parietal cells and (H+ + K+)-ATPase activity in canine gastric microsomes were investigated. Both the (+)-and the (-)-enantiomer of lansoprazole inhibited the acid formation stimulated by dibutyryl cyclic AMP (db-cAMP) in isolated canine parietal cells in a concentration-dependent manner with IC50 values of 59 and 82 nM, respectively. The enantiomers showed concentration-dependent inhibition of (H+ + K+)-ATPase with IC50 values of 4.2 and 5.2 microM, respectively. On the other hand, the IC50 values of lansoprazole for db-cAMP-stimulated acid formation and (H+ + K+)-ATPase were 59 nM and 2.1 microM, respectively. These results suggest that the two enantiomers of lansoprazole have antisecretory action due to inhibition of (H+ + K+)-ATPase.
authors.affiliation: Biology Research Laboratories, Takeda Chemical Industries Ltd, Osaka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nagaya
authors.forename: N
authors.initials: N
authors.lastname: Inatomi
authors.forename: A
authors.initials: A
authors.lastname: Nohara
authors.forename: H
authors.initials: H
authors.lastname: Satoh
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D003994:Bucladesine / Q000037:antagonists & inhibitors; D004285:Dogs; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology; D017506:H(+)-K(+)-Exchanging ATPase; D064747:Lansoprazole; D008861:Microsomes / Q000187:drug effects; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000494:pharmacology; D010295:Parietal Cells, Gastric / Q000187:drug effects* / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D064747:Lansoprazole; D003994:Bucladesine; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase; D009853:Omeprazole