Signal transduction mechanisms in developmental neurotoxicity: the phosphoinositide pathway

The importance of activation of second messenger systems which follows the interaction of neurotransmitters, hormones and growth factors with their receptors is increasingly recognized. The phosphoinositide/protein kinase C pathway has received particular attention in the past decade, particularly for its involvement in the control of intracellular calcium levels. Though new functions of this metabolic pathway in the nervous system are continuously discovered, little is still known about the possible role of phosphoinositide metabolism in mediating various aspects of neurotoxicity. Limited information also exists on various aspects of inositol metabolism during brain development and, as a consequence, on its possible role in developmental neurotoxicity. In this brief review, some of the current concepts of receptor--activated phosphoinositide metabolism, particularly during brain development, are summarized. Two examples are presented to indicate its possible involvement in developmental neurotoxicity. The acetylcholine muscarinic receptor--stimulated inositol metabolism is discussed as a potential target for the developmental neurotoxicity of ethanol. The possible contribution of the glutamate metabotropic receptors in the neurotoxicity of excitatory amino acid in the immature brain is also discussed.