EFFECTS OF ALUMINUM ON NEURONAL SIGNAL-TRANSDUCTION - MECHANISMS UNDERLYING DISRUPTION OF PHOSPHOINOSITIDE HYDROLYSIS

1. Aluminum is neurotoxic in humans and animals and alters formation o f inositol phosphate (IF) second messengers following in vivo or in vi tro exposure. 2. Several components of the IP signalling system includ ing G-proteins, phosphatidylinositol-specific phospholipase C (PI-PLC) , protein kinase C (PKC) and Ca2+ homeostasis are susceptible to inhib ition/disruption by aluminum compounds. 3. Recent evidence suggests th at, despite its effects on other components, competitive inhibition by aluminum of phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis b y PI-PLC underlies its effects on agonist-stimulated IP generation.