Mastoparan elicits prostaglandin E(2) generation and inhibits inositol phosphate accumulation via different mechanisms in rabbit astrocytes

The effects of mastoparan on phosphoinositide hydrolysis and prostaglandin E(2) (PGE(2)) generation were investigated in astrocytes cultured from rabbit brain. Mastoparan inhibited the accumulations of [H-3]inositol phosphates induced by bradykinin (1 mu M) in a time- and concentration-dependent manner. Mastoparan (3-30 mu M) also released PGE(2) in a time- and concentration-dependent manner. Mastoparan-induced release of PGE(2) was inhibited by indomethacin, a cyclooxygenase inhibitor, by dexamethasone, a steroidal anti-inflammatory drug, and by pertussis toxin, an inactivator of some G proteins, such as Gi and Go. Mastoparan also caused [H-3]arachidonic acid liberation, which was inhibited by dexamethasone or pertussis toxin. in contrast, indomethacin, dexamethasone and pertussis toxin failed to attenuate mastoparan-induced inhibition of [H-3]inositol phosphate accumulation induced by bradykinin. Thus, mastoparan-induced inhibition of phosphoinositide hydrolysis does not involve pertussis toxin-sensitive G protein nor arachidonic acid metabolites. In addition to the inhibition of phospholipase C, mastoparan activates phospholipase A(2) through pertussis toxin-sensitive G protein.