The biosynthesis of sulfated
mucin in gastric tissue was investigated in cold-stress and
indomethacin (CSI)-induced
gastric ulcer models. To examine the synthesis of gastric sulfated
mucin, [35S]H2SO4 (
sulfate) incorporation into
gastric mucin was measured. The treatment of CSI inhibited the incorporation of [35S]
sulfate after 2 hr. The gastric acid hypersecretion or the formation of severe
ulcer was observed at 1 or 4 hr after the CSI-treatment, respectively.
Pibutidine hydrochloride (IT-066), a novel H2-receptor antagonist, (0.3 mg/kg, s.c.) inhibited the formation of
ulcer and reversed the inhibition of
mucin sulfation by the CSI-treatment, whereas
atropine sulfate, a
muscarinic receptor antagonist, (1.0 mg/kg, s.c.) did not inhibit the development of
ulcer nor decrease in the
mucin sulfation at 6 hr after the CSI-treatment.
IT-066 inhibited the total
acid output (T.A.O.) due to the reduction of the acidity in the gastric juice, whereas
atropine inhibited the T.A.O. due to that of the volume. These results indicated that a different mode of action between
IT-066 and
atropine on gastric acid secretion influences their actions in the incorporation of [35S]
sulfate and the formation of
ulcer in the CSI-treated rat. Therefore, it is considered that the reduction of biosynthesis of gastric sulfated
mucin following
acid hypersecretion may be responsible for the formation of
gastric ulcer.