Unique Aspects of Muscarinic Receptor Stimulated Inositol Polyphosphate Formation in Brain: Changes in Senescence

摘要: The agonist dependent hydrolysis of membrane phosphoinositides is a major signal transduction pathway in brain (Berridge 1985; Crews et al. 1988a). A variety receptors including muscarinic cholinergic, α1-adrenergic, serotonergic, and peptides, couple to phosphoinositide via activation phospholipase C 1985, Gonzales 1985). Hydrolysis one these phosphoinositides, phosphatidylinositol 4,5-bisphosphate [PtdIns(4, 5)P2] results the formation 1,2 diacylglycerol (DAG) inositol 1,4,5-trisphosphate [Ins(1,4,5)P3], both which appear have second messenger functions (Batty al., 1989; Berridge Irvine, Rana Hokin, 1990). DAG remains where it can activate protein kinase (PKC), family calcium/phospholipid kinases, that regulate numerous cellular may play role neuronal plasticity cell death. Ins(1,4,5)P3 released into cytoplasm binds specific on endoplasmic reticulum releases intracellular Ca2+ cytoplasm. Specific phosphomonoesterases rapidly metabolize 1,4-bisphosphate, 4-monophosphate finally free sequential dephosphorylation (Fig. 1). be phosphorylated Ins(1,3,4,5)P4 by Ca2+/calmodulin sensitive 3-kinase Irvine 1986). also involved influx (Irvine 1986), release (Gawler 1990) sequestration (Hill Boynton, 1990; Boynton dephosphorylated 5-phosphatase 1,3,4-trisphosphate, an inactive isomer. In addition, cyclic phosphates are produced action phosphoinositides. accumulate prolonged stimulation but their not clear (Bansal Majerus,