Characterization of dimethylguanosine, phenylethylamine, and phenylacetic acid as inhibitors of Ca2+ ATPase in end-stage renal failure.

Journal of the American Society of Nephrology : JASN
J JankowskiH Schluter

Abstract

The activity of the plasma membrane Ca2+ ATPase of chronic renal failure patients is decreased by circulating inhibitors yet to be characterized. In this study, inhibitors of Ca2+ ATPase were isolated from ultrafiltrate of patients with end-stage renal failure. They were identified as dimethylguanosine, phenylethylamine, and phenylacetic acid by chromatography and mass spectrometry. Ca2+ ATPase activity was measured spectrophotometrically as the difference in hydrolysis of ATP in the presence and absence of Ca2+ with different concentrations of ATP and the isolated substances. All of the identified compounds are sufficiently lipophilic to penetrate the blood-brain barrier and to accumulate in cerebral tissue. The inhibitory effects of these agents were additive. The apparent K(m) values for ATP and Ca2+ were not altered by these substances, suggesting a noncompetitive mechanism of inhibition. In plasma of healthy subjects, the substances were not detectable. The Ca2+ ATPase inhibitors identified may play a role in the pathophysiology of end-stage renal failure and, potentially, in monitoring toxic effects on cellular Ca2+ metabolism in renal failure.

Citations

Feb 13, 2001·Kidney International. Supplement·J JankowskiH Schlüter
Mar 15, 2005·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·Jane DelaneyCatherine J Waterfield
Dec 20, 2005·Blood Purification·R VanholderN Lameire
Feb 22, 2008·Journal of the American Society of Nephrology : JASN·Raymond VanholderUNKNOWN European Uremic Toxin Work Group
Dec 9, 2008·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Eva SchepersRaymond Vanholder
Aug 28, 2009·Seminars in Dialysis·Noémie Jourde-ChichePhilippe Brunet
Aug 28, 2009·Seminars in Dialysis·Griet GlorieuxRaymond Vanholder
Oct 27, 2009·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Dorota Polak-JonkiszDanuta Zwolinska
Oct 1, 2010·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Dorota Polak-JonkiszDanuta Zwolińska

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