Geranylgeranylacetone and cetraxate hydrochloride increase UDP-galactosyltransferase activity in rat gastric mucosa.
UDP-galactosyltransferase (UDP-Gal-T) is a key enzyme in the synthesis of mucus glycoprotein which plays an important role in gastric mucosal defensive mechanisms. Analysis of gastric UDP-Gal-T activity should clarify the mechanisms of the action of antiulcer drugs regarding gastric defensive factors. Here, we examined UDP-Gal-T activity in rat gastric mucosa treated with the antiulcer drugs geranylgeranylacetone (GGA) and cetraxate hydrochloride (CET). The effects of coadministration of indomethacin and exogenous administration of prostaglandins (PGs) were also studied. GGA and CET significantly increased UDP-Gal-T activity, and coadministration of indomethacin inhibited the increase of enzyme activity. UDP-Gal-T activity level with GGA was significantly higher than the control level, even in the presence of indomethacin. With CET, however, this was not the case. Among PGs, PGE1 significantly increased enzyme activity. Concomitant administration of PGE1 and GGA or CET increased UDP-Gal-T activity even with indomethacin to the levels achieved when these antiulcer drugs were administered without indomethacin. Our findings suggest that GGA and CET exert antiulcer effects by increasing mucus glycoprotein synthesis and that endogenous PG synthesis may be involved in this process. However, mechanisms not mediated by endogenous PGs may also exist in the stimulatory action of GGA on UDP-Gal-T activity.
Mikami
Y
Y
First Department of Internal Medicine, Okayama University Medical School, Japan.
Mizuno
M
M
Maga
T
T
Kihara
Y
Y
Yoshinaga
F
F
Tanaka
S
S
Yunoki
N
N
Kawahara
T
T
Okada
H
H
Tsuji
T
T
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D004224:Diterpenes / Q000494:pharmacology*; D005700:Galactosyltransferases / Q000187:drug effects* / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014148:Tranexamic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D004224:Diterpenes; D011453:Prostaglandins; C000665:cetraxate; D014148:Tranexamic Acid; D005700:Galactosyltransferases; C031049:geranylgeranylacetone