Universality of Amino Acid Signaling between Diverse Plasma Cells

Abstract

Both glutamic (Glu) and gamma-aminobutyric (GABA) acids are believed to play roles as neurotransmitters released from particular neurons into synaptic clefts in the mammalian central nervous system. Although GABA has been shown to act as an extracellular signal outside the brain, little attention has been paid to the possible expression of machineries required for neuronal glutamatergic signaling in cells other than central neurons. We first demonstrated the presence of Glu receptors in peripheral tissues such as the adrenal and pituitary glands three decades ago. In this review, I will outline our experimental findings accumulated since then on the physiological and pathological significance of neuronal amino acids as an extracellular signal for the maintenance of homeostasis in a variety of plasma cells. For example, Glu is released upon stimulation in a Ca2+-dependent manner for signal output in osteoblasts, where Glu is essential for the expression of the master regulator of osteoblastogenesis through a particular inotropic receptor subtype. In contrast, GABA plays a role in mechanisms underlying the suppression of cellular differentiation and maturation through a particular metabotropic receptor subtype in osteoblasts. Taken together, osteoblastic maturation proceeds as a delicate balancing between excitatory glutamatergic and inhibitory GABAergic signals, as seen in the brain. Re-evaluation of drugs currently used could be beneficial for the efficient discovery and development of innovative drugs useful for the prophylaxis and/or therapy of a variety of diseases relevant to the disturbance of glutamatergic and GABAergic signaling in diverse plasma cells.