title: Possible involvement of glutamatergic signaling machineries in pathophysiology of rheumatoid arthritis.
abstract: The prevailing view is that L-glutamate (Glu) functions as an excitatory amino acid neurotransmitter through a number of molecular machineries required for the neurocrine signaling at synapses in the brain. These include Glu receptors for signal input, Glu transporters for signal termination, and vesicular Glu transporters for signal output through exocytotic release. Although relatively little attention has been paid to the functional expression of these molecules required for glutamatergic signaling in peripheral tissues, recent molecular biological analyses including ours give rise to a novel function for Glu as an extracellular signal mediator in the autocrine and/or paracrine system in several peripheral and non-neuronal tissues, including bone and cartilage. In particular, a drastic increase is demonstrated in the endogenous levels of both Glu and aspartate in the synovial fluid with intimate relevance to increased edema and sensitization to thermal hyperalgesia in experimental arthritis models. However, to date, there is only limited information about the physiological and pathological significance of glutamatergic signaling machineries expressed by articular synovial tissues. In this review, we have outlined the role of Glu in synovial fibroblasts in addition to the possible involvement of glutamatergic signaling machineries in the pathogenesis of joint diseases such as rheumatoid arthritis.
authors.affiliation: Laboratory of Molecular Pharmacology, Kanazawa University Graduate School of Natural Science and Technology, Kanazawa, Ishikawa, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Hinoi
authors.forename: Yukio
authors.initials: Y
authors.lastname: Yoneda
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D001224:Aspartic Acid / Q000378:metabolism; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism; D050491:Glutamate Plasma Membrane Transport Proteins / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D017470:Receptors, Glutamate / Q000378:metabolism*; D013582:Synovial Fluid / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism*; D050496:Vesicular Glutamate Transport Proteins / Q000378:metabolism*
chemical_list: D050491:Glutamate Plasma Membrane Transport Proteins; D017470:Receptors, Glutamate; D050496:Vesicular Glutamate Transport Proteins; D001224:Aspartic Acid; D018698:Glutamic Acid