Table 2.
Overview of distinctive physiological and pathophysiological functions of renal NMDARs with signaling pathways involved.
| Pharmacological Modulator | Mode of Action | Relation Function/Disease | Signaling Pathway | Reference |
|---|---|---|---|---|
| MK-801, 5,7-DCKA | Inhibition | Renal vasoconstriction | [50] | |
| Glycine | Activation | Increased RBF, diuresis, natriuresis | [83] | |
| KYNA | Inhibition | Antihypertensive action | [83] | |
| MK-801 | Inhibition | Reduction of SNGFR | [64] | |
| MSG | Activation | Increase of GFR and tubular reabsorption of Na, K | [87] | |
| NMDA | Activation | Attenuation of EMT and renal fibrosis | Ras-MEK, Snail, pSmad2/3 | [58] |
| NMDA | Activation | Decrease of 1,25(OH)2D3 synthesis | MAPK-Erk1/2 | [57] |
| NMDA | Activation | Decrease of GFR | [90] | |
| D-AP5, KYNA, KET, MgSO4, PGZ, CUR, E2 | Inhibition | Amelioration of IRI-induced AKI | ROS, PPAR-γ | [90,91,92,93,94,95] |
| MK-801 | Inhibition | Attenuation of LPS-induced endotoxemia | [96] | |
| Ligustrazine | Inhibition | Attenuation of experimental sepsis-associated AKI | [97] | |
| Nor-KA, MK-801 | Inhibition | Podocyte CSK remodeling; Increase of GAP | CaMKII, cofilin | [62] |
| NMDA | Activation | Reduction of nephrin and podocin expression; apoptosis | Akt, Erk1/2, RhoA, ROS, p47 | [61,98] |
| MK-801 | Inhibition | Attenuation of hHcys-induced GS | Nox | [59] |
| MK-801, H2S, memantine | Inhibition | Attenuation of DN | Cdc42-GTP, ROS | [60,99,100,101] |
| MK-801 | Inhibition | Amelioration of GEN-induced nephrotoxicity | Endothelin-ETRB-NO | [102] |
| Glutamate/MK-801, GLY | Activation/Inhibition | Cell damage and apoptosis | ROS | [103,104] |
D-AP5: D-2-Amino-5-phosphonopentanoic acid; 5,7-DCKA: 5,7-Dichlorokyneurenic acid; KYNA: kynurenic acid (KYNA); KET: ketamine; RBF: renal blood flow; SNGFR: single nephron glomerular filtration rate; EMT: epithelial-mesenchymal transition; MSG: monosodium glutamate; AKI: acute kidney injury; IRI: ischemia-reperfusion injury; CUR: curcumin; E2: estradiol, PGZ: pioglitazone; MgSO4: magnesium sulfate; LPS: lipopolysaccharide; nor-KA: norketamine hydrochloride; GS: glomerulosclerosis; GAP: glomerular albumin permeability; CSK: cytoskeleton; DN: diabetic nephropathy; ROS: reactive oxygen species; GEN: gentamicin; NO: nitric oxide; GLY: glyphosate.