title: Interaction of metal ions with neurotransmitter receptors and potential role in neurodiseases.
abstract: There is increasing evidence that toxic metals play a role in diseases of unknown etiology. Their action is often mediated by membrane proteins, and in particular neurotransmitter receptors. This brief review will describe recent findings on the direct interaction of metal ions with ionotropic γ-aminobutyric acid (GABAA) and glutamate receptors, the main inhibitory and excitatory neurotransmitter receptors in the mammalian central nervous system, respectively. Both hyper and hypo function of these receptors are involved in neurological and psychotic syndromes and modulation by metal ions is an important pharmacological issue. The focus will be on three xenobiotic metals, lead (Pb), cadmium (Cd) and nickel (Ni) that have no biological function and whose presence in living organisms is only detrimental, and two trace metals, zinc (Zn) and copper (Cu), which are essential for several enzymatic functions, but can mediate toxic actions if deregulated. Despite limited access to the brain and tight control by metalloproteins, exogenous metals interfere with receptor performances by mimicking physiological ions and occupying one or more modulatory sites on the protein. These interactions will be discussed as a potential cause of neuronal dysfunction.
authors.affiliation: Istituto di Biofisica, Consiglio Nazionale delle Ricerche, via De Marini, 6, 16149, Genoa, Italy, marchetti@ge.ibf.cnr.it.
authors.forename: Carla
authors.initials: C
authors.lastname: Marchetti
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002104:Cadmium / Q000633:toxicity; D002412:Cations / Q000378:metabolism*; D003300:Copper / Q000502:physiology; D004785:Environmental Pollutants / Q000633:toxicity; D006801:Humans; D007854:Lead / Q000633:toxicity; D008565:Membrane Proteins / Q000378:metabolism; D008667:Metalloproteins / Q000502:physiology; D008954:Models, Biological; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000378:metabolism; D009532:Nickel / Q000633:toxicity; D021122:Protein Subunits; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D058468:Receptors, Ionotropic Glutamate / Q000187:drug effects / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015032:Zinc / Q000502:physiology
chemical_list: D002412:Cations; D004785:Environmental Pollutants; D008565:Membrane Proteins; D008667:Metalloproteins; D021122:Protein Subunits; D011963:Receptors, GABA-A; D058468:Receptors, Ionotropic Glutamate; D017981:Receptors, Neurotransmitter; D011994:Recombinant Proteins; D002104:Cadmium; D007854:Lead; D003300:Copper; D009532:Nickel; D015032:Zinc