Prostaglandin protects isolated guinea pig chief cells against ethanol injury via an increase in diacylglycerol.
We studied cellular processes activated by prostaglandins (PG) that are involved in the protection of gastric chief cell injury estimated in terms of dye exclusion test, release of lactate dehydrogenase (LDH), or 51Cr from prelabeled chief cells. Pretreatment of chief cells with 3 x 10(-6) M PGE2 or PGE1 at 37 degrees C and pH 7.4 for 15 min maximally reduced not only ethanol- but also taurocholic acid-caused LDH release from chief cells. PGs equipotently stimulated increases in the accumulation of diacylglycerol and cyclic AMP without elevating intracellular Ca2+ concentrations in gastric chief cells. The rank order of the potency was equal to that of PGs to reduce the injury. Pretreatment of chief cells with synthetic 1-oleoyl-2-acetyl-sn-glycerol (OAG) or 12-o-tetradecanoyl phorbol 13-acetate (TPA) reduced the injury of chief cells, while 4 alpha-phorbol 12,13-didecanoate, an inactive phorbol ester, failed to reduce the injury and 1-(5-isouinolinylsulfonyl)-2-methylpiperazine (H7) blocked the protective action of PGE2. On the other hand, forskolin and dbcAMP had no effect on ethanol-caused LDH release and diacylglycerol formation in chief cells. These results suggest that PGE2 and PGE1 possess the direct protective action against ethanol- or taurocholic acid-caused injury in chief cells, presumably through the activation of the diacylglycerol/protein kinase C signaling pathway.
Konda
Y
Y
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Nishisaki
H
H
Nakano
O
O
Matsuda
K
K
Wada
K
K
Nagao
M
M
Matozaki
T
T
Sakamoto
C
C
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism* / Q000494:pharmacology; D000431:Ethanol / Q000633:toxicity*; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D010435:Pepsinogens / Q000378:metabolism; D011453:Prostaglandins / Q000494:pharmacology*; D011493:Protein Kinase C / Q000502:physiology; D013270:Stomach / Q000166:cytology* / Q000187:drug effects
D004075:Diglycerides; D010435:Pepsinogens; D011453:Prostaglandins; D005576:Colforsin; D000001:Calcimycin; D000431:Ethanol; D003994:Bucladesine; D000242:Cyclic AMP; D007770:L-Lactate Dehydrogenase; D011493:Protein Kinase C; D002118:Calcium