Inositol Lipids and Signal Transduction in the Nervous System: An Update

Abstract

The role that inositol lipids play in cellular signaling events in eukaryotic cells remains one of the most intensively investigated areas of cell biology. In this respect, phosphoinositide‐mediated signal transduction in the CNS is no exception; major advances have been made since a previous review on this subject (Fisher and Agranoff, 1987). Not only have stimulated phosphoinositide turnover and its physiological sequelae been demonstrated repeatedly in a variety of neural preparations, but, in addition, the detailed molecular mechanisms underlying these events continue to unfold. Here we review the progress that has occurred in selected aspects of this topic since 1987. In the first two sections of this article, emphasis is placed on novel functional roles for the inositol lipids and on recent insights into the molecular characteristics and regulation of three key components of the phosphoinositide signal transduction system, namely, the inositol lipid kinases, phospholipases C (PLCs), and the inositol 1,4,5‐trisphosphate[I(1,4,5)P3] receptor. The metabolic fate of I(1,4,5)P3 in neural tissues, as well as its control, is also detailed. Later we focus on identification of the multiple receptor subtypes that are coupled to inositol lipid turnover and discuss possible strategies for intervention into phosphoinositide‐mediated signal transduction. Due to space limitations, an extensive evaluation of the diacylglycerol/protein kinase C (DAG/PKC) limb of the signal transduction pathway is not included (for reviews, see Nishizuka, 1988; Kanoh et al., 1990).

Trimethyltin Stimulates Protein Kinase C Translocation Through Receptor‐Mediated Phospholipase C Activation in PC12 Cells

“…As intracellular 1P 3 can mobilize intracellular pools of calcium (Fisher et al, 1992), the role of increased free cytosolic calcium levels in the mechanism of TMT-mediated PKC translocation was investigated. TMT exposure does not increase free intracellular calcium content within 30 mm in the differentiated and undifferentiated PC 12 cell at TMT concentrations used in this study (Viviani et al, 1995;M.D.K., unpublished data).…”

Modulation of basal nitric oxide-dependent cyclic-GMP production by ambient glucose, myo-inositol, and protein kinase C in SH-SY5Y human neuroblastoma cells.

“…These well-differentiated neuronal cells selectively subcloned from the SKN-SH neuroblastoma (50) are commonly employed to study neuronal metabolism and signal transduction (51), in this case the relationship of d-glucose and MI metabolism to PKC and NO-dependent cGMP.…”

Relationship between Haemoglobin Genotype, Incidence of Diabetes Mellitus and Some Clinical Complications in Southern Nigeria Tertiary Health Institutions

“…The phosphatidylinositol cycle involves the transformation of phospholipids accompanied by cell activation, and this cycle is important for the conduction of nerve impulses [25]. Under normal conditions, the Na+/K+ ATPase activity in the nerve maintains a lower concentration of sodium in the peripheral nerves compared to the plasma [26].…”