Effect of 1,6-dihydro-2-[2-(2-methylpropoxy)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-pyrimidinecarbo xylic acid, (MAR-99, CAS 98772-05-5) (10-30 mg/kg i.g.) improved the reduction of gastric blood flow rate induced by the administration of 99.5% ethanol or acidified-acetylsalicylic 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, MAR-99 (10-30 mg/kg i.g.) improved the decrease in gastric potential difference 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 pretreatment with indomethacin. Furthermore MAR-99 (10 and 30 mg/kg p.o.) had no effect on the prostaglandins (PGE2 and I2) contents in the stomach of normal rats. In pylorus-ligated rats, MAR-99 (3-100 mg/kg i.d.) showed a weak or no effect on acidity and pepsin activity in gastric juice, although this compound decreased dose-dependently the volume of gastric juice. In perfused stomachs, MAR-99 (30-100 mg/kg i.d.) slightly prevented the acid secretion induced by carbachol and pentagastrin. However, MAR-99 did not affect the acid secretion stimulated by histamine. These results indicated that anti-ulcer effect of MAR-99 was mainly due to maintenance of the gastric mucosal resistance.
Ishizuka
Y
Y
Research Laboratories, Roussel Morishita Co., Ltd., Shiga, Japan.
Kamisaki
T
T
Okamoto
N
N
Matsuda
M
M
Shimazaki
I
I
Kimura
I
I
Kamiya
A
A
Kataoka
M
M
Kawashima
M
M
Terashima
K
K
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006595:Hexosamines / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009093:Mucus / Q000378:metabolism; D010418:Pentagastrin / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013270:Stomach / Q000098:blood supply
D000897:Anti-Ulcer Agents; D006595:Hexosamines; D011743:Pyrimidines; D000431:Ethanol; D006632:Histamine; D002217:Carbachol; C087838:MAR 99; D010418:Pentagastrin; D001241:Aspirin; D007213:Indomethacin