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D‐Aspartic acid is a novel endogenous neurotransmitter
Author(s) -
D'Aniello Salvatore,
Somorjai Ildiko,
GarciaFernàndez Jordi,
Topo Enza,
D'Aniello Antimo
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.10-168492
Subject(s) - endogeny , neurotransmitter , aspartic acid , chemistry , biochemistry , amino acid , receptor
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 norvégiens ) 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 inneurogenesis’ learning’ and neuropathologies’ our results have important implications for biomedical and clinical research.—D'Aniello, S., Somorjai, I., Garcia‐Fernàndez, J., Topo, E., D'Aniello, A. D‐Aspartic acid is a novel endogenous neurotransmitter. FASEB J. 25’ 1014–1027 (2011). www.fasebj.org