Effects of combination treatment with famotidine and methylmethionine sulfonium chloride on the mucus barrier of rat gastric mucosa.
OBJECTIVE
In Japan, peptic ulcer disease (PUD) is treated clinically with a combination of a mucosal protectant and acid suppressants, but there is scant information regarding the effects of these drugs on normal gastric mucus cells. In the present study, the effects of co-administration of methylmethionine sulfonium chloride (MMSC) and famotidine on rat gastric mucus cells were investigated using both biochemical and histological methods.


METHODS
Rats were divided into four groups: controls were given carboxymethylcellulose orally once daily for 7 days and the second, third and fourth groups were treated similarly with famotidine (famotidine group), MMSC (MMSC group) or famotidine plus MMSC (combination group). After killing the rats on the 8th day, the stomachs were removed and the biosynthesis and amount of mucin in different areas of the gastric mucosa were compared among groups. Using anti-mucin monoclonal antibodies, the mucin content and immunoreactivity were also compared.


RESULTS
Both the biosynthesis and accumulation of mucin were significantly decreased in the famotidine group, but increased in the MMSC and combination groups. The amount and immunoreactivity of surface mucus cell-derived mucin were both reduced in the famotidine group, and increased in the MMSC and combination groups. There was no difference among the groups in the content and immunoreactivity of gland mucus cell-derived mucin.


CONCLUSIONS
Famotidine-induced suppression of gastric surface mucus cell function is prevented by combined treatment with MMSC, raising the possibility of a more effective cure of PUD.
Ichikawa
Takafumi
T
Department of Biochemistry, Kitasto University School of Medcine, Sagamihara, Kanagawa, Japan. t.ichika@kitasato-u.ac.jp
Ito
Yuko
Y
Saegusa
Yoichi
Y
Iwai
Tomohisa
T
Goso
Yukinobu
Y
Ikezawa
Tomoaki
T
Ishihara
Kazuhiko
K
D000284:Administration, Oral; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D015738:Famotidine / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D005752:Gastric Mucins / Q000096:biosynthesis*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014814:Vitamin U / Q000008:administration & dosage / Q000494:pharmacology*
D000897:Anti-Ulcer Agents; D005752:Gastric Mucins; D006635:Histamine H2 Antagonists; D014814:Vitamin U; D015738:Famotidine