Ushiro T, Tsukimi Y, Tanaka H
First Department of New Drug Research Laboratories, Technical Center, Shin Nippon Pharmaceutical Inc., Kishiwada, Osaka, Japan.
Jpn J Pharmacol. 1997 Nov;75(3):303-6.
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.
我们研究了一种新合成的化合物3-氨基-5-甲基-2-(2-甲基-3-噻吩基)咪唑并[1,2-a]噻吩并[3,2-c]吡啶（SPI-447）对从猪胃黏膜分离的H⁺,K⁺-ATP酶活性的影响。在冻干的胃小泡中，SPI-447在pH 7.4的溶液中以剂量依赖性方式抑制K⁺刺激的ATP酶活性（IC50 = 4.2微摩尔（1.05 - 16.8））。SPI-447的抑制作用在pH 6.8时增强（IC50 = 1.05微摩尔（0.31 - 3.57）），且不受谷胱甘肽影响。在完整的胃小泡中，SPI-447对H⁺跨微粒体膜的自发扩散没有影响。这些结果表明，SPI-447以不依赖于巯基的方式直接抑制胃H⁺,K⁺-ATP酶活性。
