ATP a potent regulator of inositol phospholipids-phospholipase C and lipid mediators in brain cortex.

Adenosine-5'trisphosphate (ATP) is stored and co-released with various neurotransmitters but it may also act as a fast excitatory neurotransmitter trough the activation of purinoreceptor(s). In this study the effect of ATP on phospholipase C (PLC) degrading labelled PtdIns(4,5)P2 and PtdIns in brain cortex slices, brain homogenate and subcellular fractions was investigated. It was found that ATP added into brain slices activated significantly and specifically PtdIns(4,5)P2 degradation and this process was inhibited by theophylline. Moreover, ATP maintained a higher level of inositol(1,4,5)P3 radioactivity in total water-soluble inositol metabolites. However, ATP added directly for the assay of PLC into brain homogenate or subcellular fractions inhibits phosphoinositide degradation in a receptor-independent manner and suppresses conversion of Ins(1,4,5)P3 into Ins(1,4)P2. Our results indicate that ATP acting extracellularly through a purinergic receptor(s) activates PtdIns(4,5)P2 degradation and release of Ins(1,4,5)P3. ATP acting directly on PLC inhibits in a receptor-independent manner phosphoinositide degradation, and protects against liberation of lipid-derived second messengers.