EFFECT OF ETHYLPROPOXY)ANILINO]-6-OXO-5-PYRIMIDINECARBOXYLIC ACID ON GASTRIC-MUCOSAL DEFENSIVE FACTORS AND GASTRIC-SECRETION IN RATS

1,6-dihydro-2-[2-(2-methylpropoxy) anilino]-6-oxo-5-pyrimidinecarboxyl ic acid, (MAR-99, CAS 98772-05-5) (10-30 mg/kg i.g.) improved the redu ction of gastric blood flow rate induced by the administration of 99.5 % ethanol or acidified-acetylsalicyclic acid (ASA). In addition, MAR- 99 (3 x 10(-6)-3 x 10(-5) mol/l) protected dose-dependently the damage of epithelial cells induced by ulcerogenic agents such as ethanol or acidified-ASA. MAR-99 (1-10 mg/kg p.o.) prevented dose-dependently the reduction of hexosamine content in glandular stomach. Furthermore, MA R-99 (10-30 mg/kg i.g.) improved the decrease in gastric potential dif ference induced by 99.5 % ethanol and acidified-ASA. MAR-99 (10-30 mg/ kg p.o.) significantly inhibited the lesion formation induced by 99.5 % ethanol and such effect of this compound was not attenuated by the p retreatment with indometacin. Furthermore MAR-99 (10 and 30 mg/kg p. o .) had no effect on the prostaglandins (PGE(2) and I-2) contents in th e stomach of nor mal rats. In pylorus-ligated rats, MAR-99 (3-100 mg/k g i.d.) showed a weak or no effect on acidity and pepsin activity in g astric juice, although this compound decreased dose-dependently the vo lume of gastric juice. In perfused stomachs MAR-99 (30-100 mg/kg i.d.) slightly prevented the acid secretion induced by carbachol and pentag astrin. However, MAR-99 did not affect the acid secretion stimulated b y histamine. These results indicated that anti-ulcer effect of MAR-99 was mainly due to maintenance of the gastric mucosal resistance