Effects of taurocholic acid/HCl alone or after pretreatment with geranylgeranylacetone on phospholipid metabolism in rat gastric mucosa.
Changes in phospholipid metabolism in gastric mucosa caused by instillation of taurocholic acid (TCA)/HCl (80 mM/300 mM) into the stomach of rats and the effects of pretreatment with an antiulcer agent, geranylgeranylacetone (GGA), were studied after intravenous injection of radioisotope-labeled precursors. The instillation of TCA/HCl rapidly reduced the incorporation of labeled fatty acids and glycerol into phosphatidylcholine and phosphatidylethanolamine, indicating the inhibition of de novo synthesis of phospholipids. These changes were restored by 120-150 min after the TCA/HCl treatment. Pretreatment with GGA enhanced the incorporation of precursors into phosphatidylcholine immediately after the instillation of TCA/HCl. Experiments in which the mucosal lipids were labeled with fatty acids prior to the instillation of TCA/HCl showed that the degradation of cellular lipids and release of the products into the gastric lumen were induced by TCA/HCl and that these changes were not prevented by GGA. Since GGA almost completely inhibited the gastric lesions induced by TCA/HCl, the enhancement of synthesis of mucosal phosphatidylcholine induced by GGA may be involved in the prevention of gastric damage. The incorporation of labeled fatty acids into free fatty acid fraction and diacylglycerol was increased quickly by the TCA/HCl treatment, suggesting early damage to the blood vessels of the gastric mucosa; these changes were inhibited significantly by GGA.
Nishizawa
Y
Y
Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.
Sakurai
H
H
Oketani
K
K
Horie
T
T
Yamato
C
C
Moriga
M
M
D000818:Animals; D004075:Diglycerides / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D005990:Glycerol / Q000378:metabolism; D006851:Hydrochloric Acid / Q000494:pharmacology*; D008297:Male; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism; D010713:Phosphatidylcholines / Q000096:biosynthesis; D010714:Phosphatidylethanolamines / Q000096:biosynthesis; D010716:Phosphatidylinositols / Q000096:biosynthesis; D010718:Phosphatidylserines / Q000096:biosynthesis; D010743:Phospholipids / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D013656:Taurocholic Acid / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism
D004075:Diglycerides; D004224:Diterpenes; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D009829:Oleic Acids; D010169:Palmitic Acids; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010716:Phosphatidylinositols; D010718:Phosphatidylserines; D010743:Phospholipids; D014280:Triglycerides; D019301:Oleic Acid; D019308:Palmitic Acid; D013656:Taurocholic Acid; D005990:Glycerol; D006851:Hydrochloric Acid; C031049:geranylgeranylacetone