title: D-Aspartic acid is a novel endogenous neurotransmitter.
abstract: D-aspartic acid (D-Asp) is present in invertebrate and vertebrate neuroendocrine tissues, where it carries out important physiological functions and is implicated in nervous system development. We show here that D-Asp is a novel endogenous neurotransmitter in two distantly related animals, a mammal (Rattus norvegicus) and a mollusk (Loligo vulgaris). Our main findings demonstrate that D-Asp is present in high concentrations in the synaptic vesicles of axon terminals; synthesis for this amino acid occurs in neurons by conversion of L-Asp to D-Asp via D-aspartate racemase; depolarization of nerve endings with K(+) ions evokes an immediate release of D-Asp in a Ca(2+) dependent manner; specific receptors for D-Asp occur at the postsynaptic membrane, as demonstrated by binding assays and by the expansion of squid skin chromatophores; D-aspartate oxidase, the specific enzyme that oxidizes D-Asp, is present in the postsynaptic membranes; and stimulation of nerve endings with D-Asp triggers signal transduction by increasing the second messenger cAMP. Taken together, these data demonstrate that D-Asp fulfills all criteria necessary to be considered a novel endogenous neurotransmitter. Given its known role in neurogenesis, learning, and neuropathologies, our results have important implications for biomedical and clinical research.
authors.affiliation: Departament de Genètica, Institut de Biomedicina, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Salvatore
authors.initials: S
authors.lastname: D'Aniello
authors.forename: Ildiko
authors.initials: I
authors.lastname: Somorjai
authors.forename: Jordi
authors.initials: J
authors.lastname: Garcia-Fernàndez
authors.forename: Enza
authors.initials: E
authors.lastname: Topo
authors.forename: Antimo
authors.initials: A
authors.lastname: D'Aniello
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D002856:Chromatophores / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D026603:D-Aspartic Acid / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D049834:Loligo / Q000502:physiology*; D016253:Microscopy, Immunoelectron; D018377:Neurotransmitter Agents / Q000378:metabolism* / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar / Q000502:physiology*; D017459:Receptors, Amino Acid / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D013045:Species Specificity; D013572:Synaptic Vesicles / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
chemical_list: D018377:Neurotransmitter Agents; D017459:Receptors, Amino Acid; C031959:aspartic acid receptor; D018698:Glutamic Acid; D026603:D-Aspartic Acid; D000242:Cyclic AMP; D011188:Potassium