Inhibition of gastric H+, K+-ATPase by 3-amino-5-methyl-2-(2-methyl-3-thienyl)imidazo[1,2-a]thieno[3,2-c]pyrid ine, SPI-447.
We investigated the effect of a newly synthesized compound, 3-amino-5-methyl-2-(2-methyl-3-thienyl)imidazo[1,2-a]thieno[3,2-c]pyridi ne (SPI-447), on the activity of H+,K+-ATPase isolated from porcine gastric mucosa. In lyophilized gastric vesicles, SPI-447 inhibited K+-stimulated ATPase activity in a dose-dependent manner in a pH 7.4 solution (IC50=4.2 microM (1.05-16.8)). The inhibitory action of SPI-447 was enhanced at pH 6.8 (IC50=1.05 microM (0.31-3.57)) and not influenced by glutathione. In intact gastric vesicles, SPI-447 had no effect on the spontaneous diffusion of H+ across the microsomal membrane. These results indicate that SPI-447 directly inhibits gastric H+,K+-ATPase activity in a SH group-independent manner.
Ushiro
T
T
First Department of New Drug Research Laboratories, Technical Center, Shin Nippon Pharmaceutical Inc., Kishiwada, Osaka, Japan.
Tsukimi
Y
Y
Tanaka
H
H
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005456:Fluorescent Dyes; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology*; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D054328:Proton Pump Inhibitors; D011725:Pyridines / Q000494:pharmacology*; D013552:Swine
D000897:Anti-Ulcer Agents; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D007093:Imidazoles; D010710:Phosphates; D054328:Proton Pump Inhibitors; D011725:Pyridines; C110320:SPI 447