Related Experiment Video

Updated: Jun 28, 2026

A High-throughput Calcium-flux Assay to Study NMDA-receptors with Sensitivity to Glycine/D-serine and Glutamate
04:48

A High-throughput Calcium-flux Assay to Study NMDA-receptors with Sensitivity to Glycine/D-serine and Glutamate

Published on: July 10, 2018

NMDA agonists and antagonists induce renal culture cell toxicity

Jocelyn C Leung1, Natalie Ragland, Tara Marphis

  • 1Department of Pediatrics, Louisiana State University Health Sciences Center and Children's Hospital, New Orleans, Louisiana 70112, USA.

Medicinal Chemistry (Shariqah (United Arab Emirates))
|November 11, 2008
PubMed

Insights

Excessive stimulation or blockade of the NMDA receptor (NMDAR) in kidney cells can lead to cell death. This study investigated NMDAR effects on renal cell survival, revealing toxicity from both overactivation and inhibition.

Area of Science:

  • Nephrology
  • Neuroscience
  • Cell Biology

Background:

  • The NMDA receptor (NMDAR) is implicated in cell toxicity within the central nervous system.
  • NMDAR expression has been identified in the renal proximal tubule, suggesting a potential role in kidney function and pathology.

Purpose of the Study:

  • To investigate the impact of NMDAR agonists and antagonists on the survival of renal cells.
  • To determine the specific effects of NMDAR modulation on proximal tubule-like (OK) and distal tubule-like (MDCK) kidney cells.

Main Methods:

  • Utilized opossum kidney (OK) and Madin-Darby canine kidney (MDCK) cell lines to model proximal and distal tubules, respectively.
  • Administered varying concentrations of glutamate (agonist) and MK-801/CPP (antagonists) to assess cell viability and apoptosis.
  • Investigated the influence of fetal bovine serum and glycine pre-treatment on NMDAR antagonist-induced toxicity.

Main Results:

  • High-dose glutamate (10 mM) significantly increased cell death in OK cells.
  • NMDAR antagonists MK-801 and CPP induced a dose- and time-dependent increase in cell death and apoptosis specifically in OK cells.
  • Fetal bovine serum partially attenuated antagonist toxicity, while glycine pre-treatment completely protected OK cells from MK-801-induced death.

Conclusions:

  • Both excessive stimulation (high-dose glutamate) and blockade of renal NMDARs can result in proximal tubule cell death.
  • Renal NMDARs, particularly in proximal tubule cells, are sensitive to excitotoxicity and antagonist-induced toxicity.
  • Glycine acts as a cytoprotective agent against NMDAR antagonist toxicity in renal cells, highlighting a potential therapeutic avenue.

More Related Videos

Examination of Anatomical Features of Retinal Ganglion Cells Under N-methyl-D-aspartic Acid (NMDA)-induced Excitotoxicity07:11

Examination of Anatomical Features of Retinal Ganglion Cells Under N-methyl-D-aspartic Acid (NMDA)-induced Excitotoxicity

Published on: September 19, 2025

Development of Human Renal Tubular Epithelial Cell Primary Cultures in Monolayers and Three-Dimensional Conditions06:32

Development of Human Renal Tubular Epithelial Cell Primary Cultures in Monolayers and Three-Dimensional Conditions

Published on: June 13, 2025

Related Concept Videos

Drug Toxicity: Dose-Dependent Reactions01:24

Drug Toxicity: Dose-Dependent Reactions

Drug toxicities can be stratified into pharmacological, pathological, or genotoxic based on their mechanisms. The incidence and severity of these toxicities generally increase with the drug's concentration in the body and exposure time.Pharmacological toxicity is evident when the therapeutic effects of drugs overshoot into adverse reactions in a predictable, dose-dependent manner. Central nervous system (CNS) depression from barbiturates is a classic example, with effects escalating from...
Drug Toxicity: Risk factors01:24

Drug Toxicity: Risk factors

Adverse Drug Reactions (ADRs) are potential complications that arise during pharmacotherapy, influenced by multiple risk factors. Age plays a significant role; both neonates and the elderly are at heightened risk due to their respective immature and diminished metabolic and elimination processes. Gender also impacts ADRs, with females experiencing a 1.5 to 1.7-fold greater risk than males, which may be linked to pharmacokinetic, pharmacodynamic, and hormonal differences. Notably, neonates, the...
Acute Kidney Injury IV: Diagnostic Studies and Prevention01:30

Acute Kidney Injury IV: Diagnostic Studies and Prevention

Accurate diagnosis and effective prevention are critical in managing Acute Kidney Injury (AKI), which is linked to high mortality rates ranging from 10% to 80%. Timely recognition of at-risk patients and careful monitoring can significantly reduce the likelihood of kidney damage.Diagnostic Assessments:The diagnostic process starts with a comprehensive medical history to identify prerenal, intrarenal, and postrenal causes.Prerenal causes, such as dehydration, hypotension, or blood loss, should...
Drugs Affecting Neurotransmitter Synthesis01:29

Drugs Affecting Neurotransmitter Synthesis

Drugs affecting neurotransmitter synthesis can impact the adrenergic neuron and the synthesis of neurotransmitters. For example, α-methyltyrosine and carbidopa target specific enzymes involved in catecholamine synthesis. α-methyltyrosine inhibits the enzyme tyrosine hydroxylase, which converts tyrosine into dopamine. By blocking this enzyme, α-methyltyrosine reduces dopamine production and other catecholamines. Carbidopa, on the other hand, inhibits the enzyme dopa decarboxylase, which converts...
Drugs Affecting Neurotransmitter Release or Uptake01:21

Drugs Affecting Neurotransmitter Release or Uptake

Certain drugs can affect how neurotransmitters called catecholamines, are released or taken back up in the adrenergic neuron. They can have different effects on the body's sympathetic transmission. Reserpine, a natural compound found in the Rauwolfia shrub, blocks a transporter called vesicular monoamine transporter (VMAT), which leads to a buildup of catecholamines in the cell and reduces sympathetic transmission. Another drug called guanethidine works in multiple ways, including blocking...
Drugs Acting on Autonomic Ganglia: Stimulants01:23

Drugs Acting on Autonomic Ganglia: Stimulants


Ganglionic stimulants activate NM nicotinic receptors in autonomic ganglia, falling into two categories: nicotine mimetics [e.g., lobeline, dimethylpiperazine, tetramethylammonium] and muscarinic receptor agonists [e.g., muscarine, methacholine]. The first category's action is rapid and blocked by nicotinic receptor antagonists, while the second category's action is delayed and blocked by atropine-like agents. Nicotine, an alkaloid, affects the heart rate by stimulating sympathetic or...