Anti-gastric acid secretory mechanism of 1,6-dihydro-2-[2-(2-methylpropoxy)anilino]-6-oxo-5-pyrimidinecarboxylic acid. Effect on mucosal mast cell.
To clarify the anti-gastric acid secretory mechanism of 1,6-dihydro-2-[2-(2-methylpropoxy)anilino]-6-oxo-5-pyrimidinecarbo xylic acid (CAS 98772-05-5, MAR-99), the relationship between gastric acid secretion and gastric mucosal mast cell (MMC) was studied and the effect of this compound on these parameters was examined and compared with anti-allergic drugs (mast cell stabilizers) and anti-ulcer drugs. The release of histamine from MMC cultured from bone marrow and connective tissue mast cell (CTMC) isolated from peritoneal cavity was found to be induced by the addition of ethanol (final conc. 17.5%), and the inhibitory effect on histamine release from MMC is closely associated with the anti-gastric secretory effect. That is to say, MAR-99 (10(-9)-10(-7) mol/l) inhibited histamine release from MMC induced by ethanol in a concentration-dependent manner. The action of MAR-99 on MMC was more sensitive than that of CTMC. In addition, MAR-99 (100 mg/kg i.d.) suppressed gastric acid secretion. On the other hand, anti-allergic drugs (mast cell stabilizers), such as DSCG and tranilast (both 10(-7) mol/l), markedly inhibited histamine release from CTMC induced by ethanol, but these drugs (10(-8)-10(-7) mol/l) showed only a tendency to prevent the release of histamine from MMC. Furthermore these drugs (both 100 mg/ kg i.d.) had no effects on gastric acid secretion. Equally anti-ulcer drugs, such as cetraxate, teprenone and sofalcone, had no effects on histamine release from mast cells of two types and gastric acid secretion. From these results, it was suggested that MMC is closely correlated with gastric acid secretion, and the anti-gastric secretory effect of MAR-99 may mainly contribute to prevent the degranulation of MMC.
Ishizuka
Y
Y
Research Laboratories, Roussel Morishita Co., Ltd., Shiga, Japan.
Kamisaki
T
T
Sato
M
M
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D001854:Bone Marrow Cells; D002492:Central Nervous System Depressants / Q000494:pharmacology; D003238:Connective Tissue / Q000187:drug effects; D003239:Connective Tissue Cells; D003864:Depression, Chemical; D000431:Ethanol / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000166:cytology* / Q000378:metabolism*; D006636:Histamine Release / Q000187:drug effects; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D011708:Pylorus / Q000502:physiology; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000897:Anti-Ulcer Agents; D002492:Central Nervous System Depressants; D011743:Pyrimidines; D000431:Ethanol; C087838:MAR 99