ACTIVATION OF ARACHIDONOYL PHOSPHOLIPASE-A(2) IN PROSTAGLANDIN-MEDIATED ACTION OF SUCRALFATE

1. The mechanism of sucralfate-induced gastric mucosal prostaglandin g eneration was investigated using mucosal cells labeled with [C-14]chol ine and [H-3]arachidonic acid. 2. In comparison to the controls, the c ells maintained in the presence of sucralfate showed a concentration d ependent increase in lysophosphatidylcholine (LPC) synthesis and PGE2 generation. The maximal effect was attained at 25 muM sucralfate givin g a 45.7% increase in LPC and 70% increase in PGE2. 3. Pretreatment wi th indomethacin prior to sucralfate, while causing inhibition in PGE2 generation, had no effect on LPC production and led to accumulation of free arachidonic acid. In the case of pretreatment with NDGA, the suc ralfate caused increased LPC synthesis accompanied by enhanced PGE2 ge neration without free arachidonic acid accumulation. 4. The stimulator y effect of sucralfate on LPC synthesis and PGE2 generation was inhibi ted by phospholipase A2 inhibitors, mepacrine and BPB. The inhibitory effect was concentration dependent and attained maximum at 40 muM for BPB and 80 muM for mepacrine. 5. The results for the first time demons trate that the enhancement in gastric mucosal prostaglandin generation by sucralfate results from the stimulation of mucosal phospholipase A 2 for arachidonic acid release.