Modulation of inositol phospholipid metabolism by polyamines

At low concentrations of Mg²⁺, incorporation of ³²P from [γ-³²P]ATP into phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP₂) in plasma membranes isolated from human polymorphonuclear leucocytes was enhanced 2-4-fold by the polyamines spermidine and spermine. Polyamines had no effects on inositol phospholipid phosphorylation at high concentrations of Mg²⁺. At 1 mM-Mg²⁺, [³²P]PIP₂ synthesis was maximally enhanced by 2 mM-spermine and 5 mM-spermidine, whereas putrescine only slightly enhanced synthesis. Spermine decreased the EC₅₀ (concn. for half-maximal activity) [³²P]PIP or [³²P]PIP₂ synthesis. Spermine also decreased the EC₅₀ for PI in [³²P]PIP synthesis. In contrast, spermine elevated the apparent V(max.), without affecting the EC₅₀ PIP, for [³²P]PIP₂ synthesis. Spermine and spermidine also inhibited the hydrolysis of [³²P]PIP₂ by phosphomonoesterase activity. Therefore polyamines appear to activate inositol phospholipid kinases by eliminating the requirements for superphysiological concentrations of Mg²⁺. Polyamine-mediated inhibition of polyphosphoinositide hydrolysis would serve to potentiate further their abilities to promote the accumulation of polyphosphoinositides in biological systems.