The neurotoxicants strychnine and bicuculline protect renal proximal tubules from mitochondrial inhibitor-induced cell death.
Glycine-induced cytoprotection of renal proximal tubules exposed to chemical- or hypoxic/anoxic-induced cell death is shared by a few amino acid agonists of the neuronal strychnine-sensitive glycine receptor. The goal of this study was to determine if antagonists of the strychnine-sensitive glycine receptor attenuated the cytoprotective effects of glycine. Strychnine did not antagonize the cytoprotective effects of glycine in proximal tubules exposed to antimycin A. In contrast, strychnine was cytoprotective, was equipotent as glycine (EC50 = 0.4 mM), and the combination of strychnine and glycine was additive. Likewise, bicuculline and norharmane were cytoprotective but 20-50% less potent than glycine. These results suggest that glycine and strychnine act as a common site to produce proximal tubule cytoprotection, but this site does not share the same potency and agonist/antagonist properties as the neuronal strychnine-sensitive glycine receptor.
Aleo
M D
MD
Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens 30602.
Schnellmann
R G
RG
D000818:Animals; D000968:Antimycin A / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology*; D002243:Carbolines; D016923:Cell Death / Q000187:drug effects; D005998:Glycine / Q000494:pharmacology; D006247:Harmine / Q000031:analogs & derivatives / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D011817:Rabbits; D018009:Receptors, Glycine; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D013329:Structure-Activity Relationship; D013331:Strychnine / Q000494:pharmacology*
D002243:Carbolines; D018009:Receptors, Glycine; D017981:Receptors, Neurotransmitter; D006247:Harmine; D000968:Antimycin A; C010262:norharman; D007770:L-Lactate Dehydrogenase; D013331:Strychnine; D005998:Glycine; D001640:Bicuculline