Effects of antiulcer drugs on phosphatidylcholine synthesis in isolated guinea pig gastric glands.
To better understand phosphatidylcholine synthesis in the stomach, we isolated guinea pig gastric glands and examined their [3H]choline incorporation into phosphatidylcholine in response to either antiulcer drugs such as geranylgeranylacetone (GGA) and H2-receptor antagonists or agents that cause phosphatidylcholine synthesis in other tissues. [3H]Choline incorporation was stimulated by GGA, palmitate, and 12-O-tetradecanoylphorbol-13-acetate (TPA). Dibutyryl cyclic-AMP had no effect. By contrast with GGA, famotidine, ranitidine, and cimetidine equipotently inhibited [3H]choline incorporation into phosphatidylcholine. GGA, palmitate, and TPA increased phosphatidyl-[3H]choline and decreased phosphoryl-[3H]choline as compared with control in tissues that had been pulsed with [3H]choline. On the other hand, no more decrease in [3H]choline incorporation at chase periods was observed in pulse-labeled glands in response to each H2-receptor antagonist. The particulate fraction of glands that had been incubated with GGA or palmitate had more CTP-phosphocholine cytidylyltransferase activity than that of glands incubated without agents. A decrease in choline kinase activity was not observed in the cytosolic fraction of glands that had been incubated with cimetidine. These results suggest that GGA and palmitate stimulate phosphatidylcholine synthesis by activating cytidylyltransferase, and H2-receptor antagonists may affect phosphatidylcholine synthesis by inhibiting choline uptake in the gastric glands.
Nishisaki
H
H
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Sakamoto
C
C
Konda
Y
Y
Nakano
O
O
Matozaki
T
T
Nagao
M
M
Matsuda
K
K
Wada
K
K
Kasuga
M
M
D000704:Analysis of Variance; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002797:Choline Kinase / Q000187:drug effects; D003600:Cytosol / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D011494:Protein Kinases / Q000187:drug effects; D014316:Tritium
D000897:Anti-Ulcer Agents; D010713:Phosphatidylcholines; D014316:Tritium; D011494:Protein Kinases; D002797:Choline Kinase