Effects of acid-degraded products of leminoprazole on acid secretion, mucus secretion and synthesis, and indomethacin-induced damage in cell culture.
We examined the effects of four acid-degraded products of leminoprazole on [1] acid secretion by parietal cells, [2] mucus secretion and synthesis by epithelial cells and [3] indomethacin-induced damage to epithelial cells. These gastric cells were prepared from rabbit stomachs. Upon stimulation with 10 microM histamine, acid secretion by parietal cells was inhibited by leminoprazole, sulfide and 2-(isobutylmethylamino)benzylalcohol. Sulfide also inhibited dibutyryl cyclicAMP (100 microM)-stimulated secretion. However, the inhibitory effects of such compounds were observed only at high concentrations, in comparison with the antisecretory concentrations of leminoprazole. On the other hand, among acid-degraded products, only sulfide enhanced mucus secretion and synthesis by epithelial cells. The stimulatory effects of sulfide were the same as those of leminoprazole. Furthermore, the effects of sulfide as well as leminoprazole were suppressed by NG-nitro-L-arginine methyl ester (L-NAME), and L-arginine, not D-arginine, prevented the inhibition by L-NAME. In contrast, all degraded products failed to protect epithelial cells against indomethacin-induced damage. Overall, these results suggest that only the mucus-elevating effect of administered leminoprazole may be partly due to the stimulatory effects of sulfide derived from leminoprazole on mucus secretion and synthesis by epithelial cells.
Takahashi
S
S
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Tsukahara
T
T
Okabe
S
S
D000143:Acids / Q000378:metabolism*; D000818:Animals; D000897:Anti-Ulcer Agents / Q000378:metabolism*; D001562:Benzimidazoles / Q000378:metabolism*; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology*; D009093:Mucus / Q000378:metabolism*; D010295:Parietal Cells, Gastric / Q000187:drug effects* / Q000473:pathology; D011817:Rabbits
D000143:Acids; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; C089751:leminoprazole; D007213:Indomethacin