N-methyl-d-aspartate receptor activation by guanidinosuccinate but not by methylguanidine: Behavioural and electrophysiological evidence

D’Hooge, Rudi; Raes, Adam; Lebrun, P.; Diltoer, Marc; Bogaert, P.P. Van; Manil, Jacqueline; Colin, F.; Deyn, Peter Paul De

doi:10.1016/0028-3908(96)00011-1

Cited by 31 publications

(11 citation statements)

References 31 publications

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“…Both latter effects are indicative of agonist actions of GSA at the NMDA receptor. We found behavioral and electrophysiological evidence that GSA (but not MG) acts as a selective agonist at NMDA‐type excitatory amino acid receptors in a similar manner to the structurally related l ‐aspartate (33).…”

Section: Effects Of Uremic Guanidino Compounds On Amino Acid Receptorsmentioning

confidence: 82%

PROGRESS IN UREMIC TOXIN RESEARCH: Guanidino Compounds as Uremic (Neuro)Toxins

Deyn

Vanholder

Eloot

et al. 2009

Seminars in Dialysis

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Neurological and vascular impairment are important sources of morbidity in patients with renal failure. A portion of patients still suffers from uremic encephalopathy or other signs of nervous system impairment. Several reports demonstrate increased incidence of cardiac infarction and cerebrovascular accidents in chronic renal failure patients, even in those otherwise adequately dialyzed. Epileptic and cognitive symptoms are among the most typical manifestations of uremic encephalopathy. Several guanidino compounds (GCs) may play an important role in the etiology of uremic encephalopathy. Four GCs appeared to be substantially increased as well in serum, cerebrospinal fluid, and brain of uremic patients. These compounds, "uremic" GCs, are creatinine, guanidine (G), guanidinosuccinic acid (GSA), and methylguanidine. All four compounds are experimental convulsants in concentrations similar to those found in uremic brain. We described a possible mechanism for the contribution of GCs to uremic hyperexcitability, referring to the in vitro effects of uremic GCs on inhibitory and excitatory amino acid receptors. It was demonstrated that the excitatory effects of uremic GCs on the central nervous system can be explained by the activation of N-methyl-d-aspartate receptors by GSA, concomitant inhibition of gamma-aminobutyric acid type A receptors by uremic GCs, and other depolarizing effects. These effects might also indicate the putative contribution of uremic GCs to the etiology of uremic encephalopathy. In this article, we review the uremic GCs with particular attention to their neurotoxicity. We elaborate in detail on the mechanisms of action of the neurotoxic uremic GCs and summarize the kinetics of these toxins.

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Section: Effects Of Uremic Guanidino Compounds On Amino Acid Receptorsmentioning

confidence: 82%

PROGRESS IN UREMIC TOXIN RESEARCH: Guanidino Compounds as Uremic (Neuro)Toxins

Deyn

Vanholder

Eloot

et al. 2009

Seminars in Dialysis

111

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show abstract

“…Different guanidino compounds (GCs) were reported as possible uremic toxins, and the accumulation of guanidino compounds and several uremic toxins generate oxidative stress, causing further renal damage in CKD patients [36][37][38]. Recently Torremans et al [7] reported remarkable increases of urea, creatinine, GSA, guanidine, methylguanidine, symmetrical dimethylarginine, ADMA and a-ketod-GVA in the blood of PKD/Mhm rats and in human ADPKD.…”

Section: Discussionmentioning

confidence: 98%

Metabolomic profiling of the autosomal dominant polycystic kidney disease rat model

et al. 2011

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“…1), appeared to be highly increased in serum as well as the cerebrospinal fluid of uremic patients. 29,86,87 De Deyn et al 13,14 demonstrated that the excitatory effects of uremic GCs on the CNS can be due to the activation of N-methyl-D-aspartate receptors, the concomitant inhibition of (-aminobutyric acid type A receptors by uremic GCs, and other depolarizing effects.…”

Section: Guanidino Compoundsmentioning

confidence: 99%