Adenosine receptor antagonism in acute tacrolimus toxicity

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
Gwenn E McLaughlinMarcelo Egea

Abstract

Calcineurin inhibitors induce renal vasoconstriction and oliguria during acute toxicity. We previously demonstrated that the non-specific adenosine receptor antagonist theophylline improved glomerular filtration rate (GFR) and renal blood flow in the setting of acute tacrolimus (TAC) toxicity. This study was undertaken to determine which of the known adenosine receptor subtypes is responsible for the observed effect of theophylline. The GFR was measured by clearance of 51Cr-EDTA in anaesthetized, instrumented Sprague-Dawley rats at three time points: at baseline, 60 min after intravenous administration of TAC (0.05 mg/kg) or vehicle (V) and at 100 min after TAC or V. Either DMSO (n = 5) or one of the three available specific adenosine receptor subtype antagonists 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 2 mg/kg, n = 5), a selective A1 receptor antagonist, 8-(3-chlorostyryl) caffeine (CSC, 2 mg/kg, n = 4), a selective A2a receptor antagonist and 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-dihydropyridine-3,5 dicarboxylate (MRS1191, 1 mg/kg, n = 5), a selective A3 receptor antagonist, was administered intra-peritoneally prior to the final GFR measurement. Repeated measures analysis of variance was used to detect diff...Continue Reading

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Citations

Nov 23, 2013·Purinergic Signalling·Geoffrey BurnstockMatthew A Bailey
Jun 26, 2007·Journal of Renal Nutrition : the Official Journal of the Council on Renal Nutrition of the National Kidney Foundation·Davide BolignanoMichele Buemi
Mar 24, 2016·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·R ZeiserG Burnstock
Apr 12, 2017·The Journal of Pharmacy and Pharmacology·Jan Schmidt, Polonca Ferk
Jul 30, 2010·The Journal of Pharmacology and Experimental Therapeutics·Luca AntonioliCorrado Blandizzi

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