[Effect of teprenone and H2-receptor antagonists on phosphatidylcholine synthesis in the isolated guinea pig gastric glands].
To better understand the mechanism of phosphatidylcholine synthesis in the stomach, [3H] choline incorporation into phosphatidylcholine in response to the drugs which have been commonly used for treating the patients with gastric ulcer was examined using isolated guinea pig gastric glands. Teprenone stimulated [3H] choline incorporation into phosphatidylcholine in gastric glands, up to 146 +/- 11% of control (n = 6, P less than 0.05). On the other hand famotidine, ranitidine and cimetidine significantly decreased the incorporation to 73 +/- 8%, 72 +/- 11%, 67 +/- 11% of control, respectively (n = 6, P less than 0.05, P less than 0.05, P less than 0.05). When the glands were pulsed with [3H] choline followed by incubation in the presence of teprenone or each H2RA for 180 min to see the effects of the agents on the limiting step of the phosphatidylcholine synthesis, teprenone also significantly stimulated [3H] choline incorporation into phosphatidylcholine, but each H2RA did not affect phosphatidylcholine biosynthesis any more. Teprenone stimulated CTP:phosphocholine cytidylyltransferase (CTF) from a basal value of 0.92 +/- 0.10 to 1.69 +/- 0.39 (nmol/min/mg protein) (n = 3, P less than 0.05). These results suggest that teprenone may stimulate phosphatidylcholine biosynthesis through the activation of CTF, a late-limiting enzyme of PC biosynthesis, and H2RA may affect phosphatidylcholine synthesis by inhibiting choline transport or choline kinase in gastric glands.
Nishisaki
H
H
Second Department of Internal Medicine, Kobe University School of Medicine.
Sakamoto
C
C
Konda
Y
Y
Nakano
O
O
Matsuda
K
K
Wada
K
K
Nagao
M
M
Matozaki
T
T
D000818:Animals; D000897:Anti-Ulcer Agents; D019916:Choline-Phosphate Cytidylyltransferase; D002927:Cimetidine / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology*; D015738:Famotidine / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006168:Guinea Pigs; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009713:Nucleotidyltransferases / Q000378:metabolism; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D011899:Ranitidine / Q000494:pharmacology
D000897:Anti-Ulcer Agents; D004224:Diterpenes; D006635:Histamine H2 Antagonists; D010713:Phosphatidylcholines; D015738:Famotidine; D002927:Cimetidine; D011899:Ranitidine; D009713:Nucleotidyltransferases; D019916:Choline-Phosphate Cytidylyltransferase; C031049:geranylgeranylacetone