Differential stimulation of PGE2 synthesis in mesangial cells by angiotensin and A23187

The mechanism of arachidonic acid release and prostaglandin E2 (PGE2) synthesis was studied in cultured mesangial cells from rat kidneys. Both the ionophore A23187 and angiotensin II stimulated radioimmunoassayable PGE2 synthesis. The effect of angiotensin occurred within minutes, with half-maximal stimulation around 10(-9) M. In cells prelabeled with [14C]arachidonate, A23187 caused release of [14C]-arachidonate from all phospholipids. In contrast, angiotensin II caused preferential release of [14C]arachidonate from phosphatidylinositol, associated with a significant increase in 14C-labeled phosphatidic acid, mono- and diacylglyceride, and arachidonate. These results indicate that angiotensin preferentially, but not exclusively, stimulates a phosphatidylinositol-specific phospholipase C, whereas A23187 results in unspecific stimulation of phospholipases. The tight coupling between an angiotensin-responsive phospholipid-arachidonate pool and cyclooxygenase may be responsible for the specificity of the response to angiotensin.