Abstract
Although the new histamine H 2 receptor antagonist, lafutidine (FRG-8813), N-[4-[4-(piperidinylmetriyl)pyridyl-2-oxy]-(Z)-2-butenyl]-2-(furfurylsulfinyl)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 N G-nitro-L-arginine (10 −5M) or 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazolme-l-oxyl-3-oxide (10 −5M), The inhibitory action of N G-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.
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