Lafutidine-induced stimulation of mucin biosynthesis mediated by nitric oxide is limited to the surface mucous cells of rat gastric oxyntic mucosa.
Although the new histamine H2 receptor antagonist, lafutidine (FRG-8813), N-[4-[4-(piperidinylmethyl)pyridyl-2-oxy]-(Z)-2-butenyl]-2-(fur furylsulfinyl)acetamide accelerates mucin metabolism of rat gastric mucosa, the physiological mechanisms by which this drug stimulates the biosynthesis remain unclear. In this paper, we report the effect of lafutidine on mucin biosynthesis in distinct sites and layers of rat gastric mucosa, including the possible participation of nitric oxide (NO). Lafutidine enhanced [3H]glucosamine incorporation into the mucin in the full thickness corpus mucosa, but not in the antrum. This stimulation on mucin biosynthesis disappeared by the removal treatment of surface mucosal cells. The lafutidine-induced increase of [3H]-labeled mucin in the corpus was completely blocked by either NG-nitro-L-arginine (10[-5] M) or 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazolne-1-oxyl-3-oxide (10[-5] M). The inhibitory action of NG-nitro-L-arginine was totally reversed by L-arginine (5 x 10[-3] M). These results suggest that the lafutidine-induced stimulation of mucin biosynthesis mediated by NO is limited to the surface mucous cells of rat gastric oxyntic mucosa.
Ichikawa
T
T
Department of Biochemistry, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
Ishihara
K
K
Saigenji
K
K
Hotta
K
K
D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D005944:Glucosamine / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D009077:Mucins / Q000096:biosynthesis*; D017942:Nitric Acid / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010880:Piperidines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical
D000081:Acetamides; D001565:Benzoates; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D006635:Histamine H2 Antagonists; D007093:Imidazoles; D009077:Mucins; D010880:Piperidines; D011725:Pyridines; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D017942:Nitric Acid; C076948:lafutidine; D019001:Nitric Oxide Synthase; D005944:Glucosamine