Abstract
The gastric phospholipid flippase has been found in isolated gastric vesicles. Fluorescence analogues of phospholipid and endogenous phospholipids were translocated from the outer to inner leaflet of the lipid bilayer membrane of hog gastric vesicles in an ATP-dependent manner. Previously we found that the flippase activity in gastric vesicles was inhibited by a K+-competitive specific inhibitor of the gastric H+, K+-ATPase, 2-methyl-8- (phenylmethoxy) imidazo [1, 2-a] pyridine-3-acetonitoril (SCH 28080). Here, we studied effects of other gastric proton pump inhibitors on the flippase activity. We found that another K+-competitive specific inhibitor of the gastric H+, K+-ATPase, 3-amino-5-methyl-2- (2-methyl-3-thionyl) imidazo [1, 2-a] thieno [3, 2-c] pyridine (SPI-447) also inhibited the flippase activity. A substituted benzimidazole-related gastric H+, K+-ATPase inhibitor, 2- {[4- (3-methoxypropoxy) -3-methylpyridin-2-ly] methylsulfinyl}-1H-benzimidazole (rabeprazole) decreased the phospholipid flippase activity to 80.6 ± 14.8% (n = 3) of the control level whereas it decreased the proton pump K+-ATPase activity to 5.6 ± 3.4% (n = 3) of the control level. These results indicated a possibility that the phospholipid flippase activity of hog gastric vesicles is part of the H+, K+-ATPase reaction, although further studies are required to confirm this possibility.
