Possible mechanism of increase in gastric mucosal PGE2 and PGI2 generation induced by ecabet sodium, a novel gastroprotective agent.

Abstract

The gastroprotective agent ecabet sodium (ecabet, 12-sulfodehydroabietic acid monosodium salt) increases the formation of prostaglandin (PG) E2 and I2 by gastric mucosa. In the present study, we examined the effect of ecabet on metabolism of arachidonic acid (AA) in rat gastric mucosal cells. Ecabet (0.1-10 mM) concentration- and time-dependently potentiated the release of [14C]AA from gastric mucosal cells prelabeled with [14C]AA and simultaneously increased the production of PGE2 and PGI2. The ecabet-mediated increases in [14C]AA release and PGE2 production were both partly depressed by mepacrine (30 and 100microM) and Ca2+ chelation. Ecabet, however, showed no effect on gastric phospholipase A2 (PLA2) activity and [Ca2+]i in the gastric mucosal cells. Ecabet and other dehydroabietic acid derivatives, 12-carboxydehydroabietic acid monosodium salt and mono[16-(12-sulfodehydroabietyl)]succinic acid monosodium salt, which potentiated the liberation of [14C]AA, increased the membrane fluidity of gastric mucosal cells assessed by using diphenylhexatrienepropionic acid (DPH-PA) as the probe, while 12-sulfamoyldehydroabietic acid showed no effect on either the AA liberation or the membrane fluidity. Ecabet (0.1-10 mM) increased the membrane fluidity concentration- and time-dependently in accordance with its facilitating effect on AA release. In conclusion, ecabet increases the synthesis of PGE2 and PGI2 by gastric mucosal cells through promoting the release of AA, which is partly dependent on PLA2 and Ca2+. The ecabet-induced increase in membrane fluidity may be involved in part in the liberation of AA from the gastric mucosal cells.