1. Ca2+ and phosphatidylinositol second messenger systems
Ca2+ and phosphatidylinositol second messenger systems. Most extracellular messengers act on these systems, as they do on the cAMP and cGMP systems, through interactions with neurotransmitter receptors (R). However, some drugs, such as Ca2+ channel blockers and lithium, can influence these systems directly. G proteins (typically Gq) are coupling factors that mediate the ability of neurotransmitter receptors to regulate phospholipase C (PLC), which metabolizes phosphatidylinositol (PI) to form inositol triphosphate (IP3) and diacylglycerol (DAG). IP3 acts to increase intracellular levels of free Ca2+ by releasing Ca2+ from internal stores. Increased levels of intracellular Ca2+ also result from the flux of Ca2+ across the plasma membrane stimulated by nerve impulses and certain neurotransmitters. The brain contains two major classes of Ca2+-dependent protein kinases. One is activated by Ca2+ in conjunction with the Ca2+-binding protein calmodulin (CaM-kinase), and the other, protein kinase C (PKC), is activated by Ca2+ in conjunction with DAG and various phospholipids. Many of these kinases have broad substrate specificities (as indicated by the multiple arrows in the figure). Phosphorylation of substrate proteins, or third messengers, by these various Ca2+-dependent protein kinases, alters their physiologic activity and either directly or indirectly triggers biologic responses to extracellular messengers.
Source: Signal Transduction in the Brain, Molecular Neuropharmacology: A Foundation for Clinical Neuroscience, 3e
Citation: Nestler EJ, Hyman SE, Holtzman DM, Malenka RC. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience, 3e; 2015 Available at: Accessed: October 30, 2017
Copyright © 2017 McGraw-Hill Education. All rights reserved