PANCREATIC-TYPE PHOSPHOLIPASE A(2), ACTIVATES PROSTAGLANDIN E(2) PRODUCTION IN RAT MESANGIAL CELLS BY RECEPTOR-BINDING REACTION

Our earlier studies have shown that mammalian pancreatic group I phospholipase A, (PLA(2)-I) has its specific receptor (PLA(2) receptor) on a wide range of mammalian cells and that the receptor-binding capability of PLA(2)-I is a property of this molecule separable from its enzymatic activity. To clarify whether PLA(2) activity is required for eliciting a biological response via the receptor or not, we examined the enzymatic activity of PLA(2)-I/PLA(2) receptor complex and the inducibility of prostaglandin (PG) E(2) production in rat mesangial cells by mutant PLA(2)s-I. Using a recombinant soluble PLA(2) receptor, we first found that PLA(2)-I could not hydrolyze a phospholipid substrate when complexed with the receptor. In the next experiment using various mutant porcine PLA(2)s-I, we found that PGE(2) production in rat mesangial cells could be induced by a mutant PLA(2)-I which retained the receptor-binding activity but had almost completely lost its enzymatic activity. These findings indicate that the enzyme action of PLA(2)-I is not required for a PLA(2)-I-induced biological response, i.e., the augmentation of PGE(2) production in rat mesangial cells.