The potential of targeting NMDA receptors outside the CNS

Introduction: NMDA receptor (NMDAR) is an ionotropic glutamate receptor with a high permeability to calcium and a unique feature of controlling numerous calcium-dependent processes. Apart from being widely distributed in the CNS, the presence of NMDAR and its potential significance in a variety of non-neuronal cells and tissues has become an interesting research topic. Areas covered: The current review summarizes prevailing knowledge on the role of NMDARs in the kidney, bone and parathyroid gland, three main organs responsible for calcium homeostasis, as well as in the heart, an organ whose function is highly dependable on balanced intracellular calcium concentrations. The review also examines studies that have advanced our understanding of the therapeutic potential of NMDAR agonists and antagonists in renal, cardiovascular and bone pathologies. Expert opinion: NMDARs have a preeminent role in many physiological and pathological processes outside the CNS. In certain organs and/or disease conditions, activating the NMDAR leads to beneficial effects for the target organ, whereas in other diseases cell signaling downstream of NMDAR activation can exacerbate their pathology. Therefore, targeting NMDARs therapeutically is rather intricate work, and surely requires more extensive investigation in order to properly tune up the diverse NMDAR's actions translating them into beneficial cellular responses.