Postreceptor Signal-Transduction Systems as Potential Targets of Lithium

  • Y. Odagaki
  • N. Nishi
  • T. Koyama


All cells have the capacity to receive external information and to transduce it to intracellular signals ending in physiological responses specific to the cell type. The rapid advance in neuroscience has elucidated the molecular mechanisms underlying such transmembrane signaling pathways. The extra-cellular information transmitted by hormones, neurotransmitters, and neuromodulators is recognized by specific protein molecules at the cell surface (receptors), which constitute ion channels themselves or modulate intracellular enzymatic machinery, resulting in alteration of second-messenger levels via guanine nucleotide-binding regulatory (G) proteins. The former type of receptor, the ligand-gated ion channels, also known as ionotropic receptors, includes nicotinic acetylcholine, serotonin3 (5-HT3), γ-aminobutyric acidA (GABAA), and excitatory amino acid receptors, such as N-methyl-D-aspantate (NMDA), α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA), and kinate subtypes, that respond to the agonist-induced stimulation within milliseconds. The latter type of receptor, the G-protein-coupled or metabotropic receptors, includes adrenergic, serotonergic (except for 5-HT3 receptors), dopaminergic, muscarinic acetylcholine, opioid, adenosine, GABAB, metabotropic glutamate, and many neuropeptide receptors. This type of receptor couples with second-messenger-generating enzymes, such as adenylyl cyclase, phospholipase C, cyclic guanosine monophosphate (GMP) phosphodiesterase, and phospholipase A2, as well as several ion channels, through the respective G proteins, thus mediating much slower signaling than the ionotropic receptors.


Lithium Treatment Adenylyl Cyclase Activity Phosphoinositide Metabolism Adenylyl Cyclase System Phosphoinositide Turnover 


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Copyright information

© Springer-Verlag Tokyo 1998

Authors and Affiliations

  • Y. Odagaki
    • 1
  • N. Nishi
    • 1
  • T. Koyama
    • 1
  1. 1.Department of PsychiatryHokkaido University School of MedicineSapporo, Hokkaido 060Japan

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