Effect of phenobarbital on metabolism of polyphosphoinositides of rat brain synaptosomes.

Synthesis and degradation of polyphosphoinositides in a rat brain synaptosome preparation were depressed by phenobarbital. Phosphatidylinositol-4-phosphate kinase (PIP-kinase), the enzyme which synthesizes phosphatidylinositol-4,5-bisphosphate (PIP2) was most strongly affected (50% inhibition at 3 mM phenobarbital); phosphatidylinositol (PI-kinase) followed (50% at 15 mM). The phosphoesterases were less sensitive: PIP-monoesterase (50% at 39 mM), PIP2-monoesterase (at 47 mM), and, least inhibited, PIP-diesterase (50% at 65 mM) and PIP2-diesterase (at 68 mM). Phenobarbital by inhibiting PIP-kinase may reduce the membrane concentration of PIP2 and thus dampen the stimulus-response which leads to the hydrolysis of PIP2 and the formation of the second messenger, inositol-1,4,5-trisphosphate (IP3), involved in mobilization of intracellular Ca2+.