LAFUTIDINE-INDUCED STIMULATION OF MUCIN BIOSYNTHESIS MEDIATED BY NITRIC-OXIDE IS LIMITED TO THE SURFACE MUCOUS CELLS OF RAT GASTRIC OXYNTICMUCOSA

Although the new histamine H-2 receptor antagonist, lafutidine (FRG-88 13), 2-oxy]-(Z)-2-buteny]-2-(furfurylsulfinyl)acetamide accelerates mu cin metabolism of rat gastric mucosa, the physiological mechanisms by which this drug stimulates the biosynthesis remain unclear. In this pa per, we report the effect of lafutidine on mucin biosynthesis in disti nct sites and layers of rat gastric mucosa, including the possible par ticipation of nitric oxide OVO). Lafutidine enhanced [H-3]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-indu ced increase of [H-3]-labeled mucin in the corpus was completely block ed by either N-G-nitro-L-arginine (10(-5) M) or nyl)-4,4,5,5-tetrameth ylimidazoline-1-oxyl-3-oxide (10(-5) M). The inhibitory action of N-G- nitro-L-arginine was totally reversed by L-arginine (5 x 10(-3) M). Th ese results suggest that the lafutidine-induced stimulation of mucin b iosynthesis mediated by NO is limited to the surface mucous cells of r at gastric oxyntic mucosa. (C) 1998 Elsevier Science Inc.