Stimulation of mucin biosynthesis in rat gastric mucosa by FRG-8813 and its structural analogs.
Certain chemical properties, which may determine the stimulatory actions of the new histamine H2 receptor antagonist, FRG-8813 (2-(furfurylsulfinyl)-N-(4-[4-(piperidinomethyl)-2-pyridyl]o xy-(Z)- 2-butenyl)acetamide), on mucin biosynthesis, were identified by considering the derivation of this drug using an organ culture system of the rat stomach. [3H]Glucosamine and [35S]sulfate incorporation was stimulated in the corpus region by FRG-8813 and its structural analog, compound A (N-[4-[[4- (piperidinylmethyl)pyridyl]-2-oxy]-(Z)-2-butenyl]phthalimide). The chronotropic response to histamine in the guinea pig right atria was suppressed by FRG-8813 in a concentration-dependent fashion. In contrast, compound A did not suppress the histamine-induced response. Ranitidine at 10(-4) M did not suppress the FRG-8813-induced increase in [3H]glucosamine incorporation into mucin. These results suggest that the pyridine derivative and amide structure are chemically important in FRG-8813 as a stimulant on mucus metabolism. Also, this effect is not directly due to histamine H2 receptor antagonism.
Ichikawa
T
T
Department of Biochemistry, Kitasato University School of Medicine, Kanagawa, Japan.
Ishihara
K
K
Shibata
M
M
Yamaura
T
T
Saigenji
K
K
Hotta
K
K
D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D008297:Male; D009077:Mucins / Q000096:biosynthesis*; D009924:Organ Culture Techniques; D010880:Piperidines / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism; D011706:Pyloric Antrum / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000081:Acetamides; D006635:Histamine H2 Antagonists; D009077:Mucins; D010880:Piperidines; D011506:Proteins; D011725:Pyridines; C076948:lafutidine