ACROSOME REACTION STIMULATED BY THE GTP NON-HYDROLIZABLE ANALOG GTP-GAMMA-S IS BLOCKED BY PHOSPHOLIPASE A(2) INHIBITORS IN HUMAN SPERMATOZOA

Phospholipase A(2) (PLA(2), EC 3.1.1.4) is involved in the cascade of signalling events leading to the acrosome reaction in human spermatozo a. In order to study the role of PLA(2) in the acrosome reaction trigg ered by GTP gamma S, a non-hydrolizable analogue of GTP, two well-know n PLA(2) inhibitory reagents were used: dexamethasone (1 mM, a synthet ic glucocorticoid), and 2-(p-amylcinnamoyl)amino-4-chlorobenzoic acid (ONO-RS-082, 320 mu g/ml). Normal human spermatozoa were incubated for 3 h under capacitating conditions and treated with several reagents [ GTP gamma S, dexamethasone, ONO-RS-082, arachidonic acid (AA) and lyso phosphatidylcholine (LPC)], alone or in different combinations. In con firmation of earlier reports, GTP gamma S induced the acrosome reactio n. On the other hand, dexamethasone and ONO-RS-082 were both able to i nhibit the acrosome reaction induced by GTP gamma S. However, when AA or LPC was added after dexamethasone or ONO-RS-082, the acrosome react ion reached values close to those obtained using GTP gamma S alone. It is concluded that PLA(2) probably plays an active role in the acrosom e reaction triggered by GTP-binding proteins.