Effect of phenobarbital on metabolism of polyphosphoinositides of rat brain synaptosomes

Abstract

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 (PIP 2) 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), PIP 2-monoesterase (at 47 mM), and, least inhibited, PIP-diesterase (50% at 65 mM) and PIP 2-diesterase (at 68 mM). Phenobarbital by inhibiting PIP-kinase may reduce the membrane concentration of PIP 2 and thus dampen the stimulus-response which leads to the hydrolysis of PIP 2 and the formation of the second messenger, inositol-1,4,5-triphosphate (IP 3), involved in mobilization of intracellular Ca 2+.