Effects of 3, 4, 5trimethoxy-N-(3-piperidyl) benzamide (KU-54) on the incorporation (excretion) of ¹⁴C-glucosamine in the gastric mucosa and the liver of rats

Abstract

Effects of KU-54 on the biosynthesis of glycoprotein in the gastric mucosa and the liver, as measured by the rate of incorporation of ¹⁴C-glucosamine, were investigated in rats under various conditions after a single administration of ¹⁴C-glucosamine (9.88 μCi/animal, ip). ¹⁴C-glucosamine was incorporated with relative ease in the acid-insoluble fraction of the gastric mucosa. KU-54 at 100 mg/kg was orally administered twice daily for 5 days in rats (though it was given once on the 5 th day) before injection of ¹⁴C-glucosamine. The rate of ¹⁴C-glucosamine incorporation into the acid-insoluble fraction of the gastric mucosa was significantly increased by KU-54, but that of the hepatic tissue was not increased. In addition, hydrocortisone (20 mg/kg) also produced a drop of incorporation of ¹⁴C-glucosamine in the gastric mucosa, but oral KU-54 at 100 mg/kg twice daily for 5 days (though it was given once on the 5 th day) significantly inhibited the drop of incorporation of ¹⁴C-glucosamine in the gastric mucosa, but that in the hepatic tissue was not inhibited. Therefore, the effects of KU-54 were greater in the gastric mucosa than in the hepatic tissue. On the 5 th day of the ulcer produced by acetic acid in rats, the specific radioactivity in the mucosa of the margin of the ulcer increased significantly compared with that in the normal (non-ulcerative) mucosa, but this phenomenon was not affected by KU-54. On the 10 th day of the ulcer produced by acetic acid, the increase of specific radioactivity in the marginal mucosa disappeared in the control group; but in the KU-54 (100 mg/kg, p.o.)-dosing group, the specific radioactivity in the marginal mucosa increased successively and significantly compared with the non-ulcerative mucosa. On the other hand, the incorporated radioactivity in the gastric mucosa reduced gradually at 24 or 48 hr after ¹⁴C-glucosamine dosing and oral KU-54 at 100 mg/kg did not affect the rate of reduction of radioactivity in both the acid-soluble and the acid-insoluble fraction of the gastric mucosa.