Regulation of prostaglandin production in cultured gastric mucosal cells.
The aims of this study were to investigate whether exogenous prostaglandin modulates prostaglandin biosynthesis by cultured gastric mucosal cells, and to clarify the role of cyclic nucleotides in the possible modulation of prostaglandin production. After pretreatment for 30 min with buffer alone (control) or 1 to 100ng/ml PGE2, cells were incubated with 4 uM arachidonic acid for 30 min. Pretreatments with greater than 5ng/ml PGE2 inhibited arachidonate-induced PGE2 and PGI2 production in a dose-dependent fashion, as compared with control, with inhibition by 64 +/- 8% and 75 +/- 4% respectively, at 100ng/ml PGE2. PGE2, at 100ng/ml, significantly increased intracellular cAMP accumulation, but pretreatment with dibutyryl cAMP (0.01-mM) did not alter the amounts of arachidonate-induced PGE2 production. Furthermore, while greater than 10ng/ml PGE2 increased cGMP production dose-dependently, preincubation with dibutyryl cGMP (0.001-0.1mM) also failed to affect PGE2 synthesis significantly. In addition, pretreatment with isobutyl-methyl-xanthine, while increasing accumulation of cellular cyclic nucleotides, did not significantly change PGE2 production. Calcium ionophore A23187-induced PGE2 production was also inhibited by pretreatment with PGE2. These results indicate that exogenous PG inhibits subsequent arachidonate or A23187-induced PG biosynthesis in rat gastric mucosal cells, and suggest the possibility that PG regulates its own biosynthesis via feedback inhibition independent of cyclic nucleotides in these cells.
Hiraishi
H
H
2nd Dept. of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Terano
A
A
Ota
S
S
Ivey
K J
KJ
Sugimoto
T
T
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology / Q000502:physiology; D006152:Cyclic GMP / Q000494:pharmacology / Q000502:physiology; D015232:Dinoprostone / Q000096:biosynthesis; D005260:Female; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism*; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D001095:Arachidonic Acids; D011453:Prostaglandins; D016718:Arachidonic Acid; D000001:Calcimycin; D000242:Cyclic AMP; D006152:Cyclic GMP; D015232:Dinoprostone