Chapter 1 Ligand-stimulated turnover of inositol lipids in the nervous system

Abstract

The stimulated turnover of inositol-related lipids (STI) following ligand interaction with plasma membrane receptor sites is common to numerous hormones, neurotransmitters, and modulators in a variety of tissues. The initial metabolic consequence of receptor–ligand interaction is an increased breakdown of phosphatidylinositol 4,5-bisphosphate (PIP 2 ) via a Ca 2+ -dependent phosphodiesterase, yielding diacylglycerol (DG) and inositol trisphosphate (IP 3 ), each of which may affect protein phosphorylation: the DG moiety by direct activation of protein kinase C and the IP 3 moiety indirectly through the liberation of intracellular Ca 2+ stores. Under conditions in which STI has been observed via 32 P i incorporation into lipids, no increase in de novo lipid synthesis is seen—a finding that supports the concept of a regenerative cycle. The STI is seen in whole brain ( in vivo ), brain slices, subcellular fractions, and in two central nervous system (CNS)-related tissues—the pineal and anterior pituitary. In the peripheral nervous system, both the superior cervical ganglion and adrenal medulla support a readily demonstrable STI. Recently there has been much interest in the ligands that support STI in transformed cell lines of neural origin—for example, neuroblastoma and astrocytoma.