Receptor-Mediated Release of Inositolphosphates in Brain Slices

Target-cell response to a number of neurotransmitters, growth factors, hormones, and other stimuli are initiated by cell-surface receptor-mediated activation of phospholipase C (PLC) and the rapid hydrolysis of phosphoinositides (1 –3 ). The activation of PLC by receptors for most neurotransmitters and growth factors occurs through a mechanism involving a guanine nucleotide regulatory protein or G protein. The PLC-catalyzed hydrolyses of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) results in the formation of inositol 1,4,5 trisphosphate (Ins(l,4,5)P3) and diacylglycerol (DAG). Both Ins(l,4,5)P3 and DAG have second-messenger functions inside the cell. Ins(l,4,5)P3 mobilizes intracellular Ca²⁺ by binding to specific intracellular receptors that promote opening of calcium channels in vesicular storage sites associated with endoplasmic reticulum (4 ,5 ), whereas DAG binds to and activates protein kinase C (PKC), resulting in the phosphorylation of a number of intracellular proteins (1 ,2 ).