Abstract
N-Methyl-d-aspartate receptor (NMDAR) is a glutamate-gated ionotropic receptor that intervenes in most of the excitatory synaptic transmission within the central nervous system (CNS). Aside from being broadly distributed in the CNS and having indispensable functions in the brain, NMDAR has predominant roles in many physiological and pathological processes in a wide range of non-neuronal cells and tissues. The present review outlines current knowledge and understanding of the physiological and pathophysiological functions of NMDAR in the kidney, an essential excretory and endocrine organ responsible for the whole-body homeostasis. The review also explores the recent findings regarding signaling pathways involved in NMDAR-mediated responses in the kidney. As established from diverse lines of research reviewed here, basal levels of receptor activation within the kidney are essential for the maintenance of healthy tubular and glomerular function, while a disproportionate activation can lead to a disruption of NMDAR’s downstream signaling pathways and a myriad of pathophysiological consequences.
Highlights
Glutamate-gated receptors (GluRs) are broadly expressed in the central nervous system (CNS) and have paramount roles in excitatory synaptic transmission and synaptic plasticity [1]
Over the past two decades, various studies reported the presence of N-methyl-d-aspartate receptor (NMDAR) in the kidney and its versatile roles in different physiological and pathological processes
It seems clear that NMDAR has important roles in proximal tubular reabsorption and glomerular filtration, as well as in the preservation of the epithelial phenotype of renal tubular epithelial cells
Summary
Glutamate-gated receptors (GluRs) are broadly expressed in the central nervous system (CNS) and have paramount roles in excitatory synaptic transmission and synaptic plasticity [1]. The N-methyl-d-aspartate receptor (NMDAR) is a glutamate-gated non-selective cation channel [1] with a particular molecular structure and specific pharmacological and functional properties [2,7,8]. NMDAR performs a multitude of normal physiological functions within the CNS [10,11,12,13] It is implicated in the alterations observed in various diseases of the brain [14]. Survival of many types of neurons strongly depends on physiological levels of NMDAR activity [12], while complete absence [12] or abnormal expression levels or altered function of this receptor have been implicated in different neurological diseases and pathological conditions [15]. The current review explores contemporary knowledge and understanding of physiological and pathophysiological functions of NMDAR in the kidney and focuses on recent findings related to signaling pathways involved in NMDAR-mediated responses in the kidney
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