Effects of the new histamine H2 receptor antagonist, FRG-8813, on gastric mucin in rats with or without acidified ethanol-induced gastric damage.
It is not presently well understood whether the histamine H2 receptor antagonist has a function other than the inhibition of gastric acid secretion, such as the effect on the gastric mucosal defence mechanism. In this paper, we report the effect of FRG-8813 (N-[4-[4-(piperidinylmethyl)pyridyl-2-oxy]-(Z)-2-butenyl]-2- (furfurylsulfinyl) acetamide), a new histamine H2 receptor antagonist, on the rat gastric mucin content with or without 0.15N HCl-ethanol (60 %)-induced gastric damage. The prior administration of FRG-8813 significantly inhibited the occurrence of macroscopically observable hemorrhagic lesions induced by the acidified ethanol treatment. Using a newly developed biochemical method, the mucin content of the deep corpus and antral mucosa of the acidified ethanol-treated animals was significantly reduced to 50% and 32% of the control, respectively. These reductions were inhibited by the pretreatment with FRG-8813. Total mucin content in the entire stomach recovered to about 80% of the control value after pretreatment with FRG-8813. A single oral administration of FRG-8813 (30 mg/kg) caused no significant change in the total mucin content, but mucin in the adherent mucus gel layer selectively and significantly increased to 250% of the control. These results suggest that FRG-8813 not only inhibits acid secretion but may also affect the gastric mucosal defensive mechanism as well.
Ichikawa
T
T
Department of Biochemistry, Kitasato University School of Medicine, Kanagawa, Japan.
Ishihara
K
K
Komuro
Y
Y
Kojima
Y
Y
Saigenji
K
K
Hotta
K
K
D000081:Acetamides / Q000494:pharmacology* / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D000431:Ethanol / Q000633:toxicity; D005752:Gastric Mucins / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D011292:Premedication; D011725:Pyridines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy*
D000081:Acetamides; D005752:Gastric Mucins; D006635:Histamine H2 Antagonists; D010880:Piperidines; D011725:Pyridines; D000431:Ethanol; C076948:lafutidine