TY - JOUR
T1 - A novel low-affinity strychnine binding site on renal proximal tubules
T2 - Role in toxic cell death
AU - Miller, Gary W.
AU - Schnellmann, Rick G.
N1 - Funding Information:
This work was supportedb y NIH grant ES-04410T. he authors would litkoe thank TheresaJ. Crossf or here xcellent technical assistance. Poofr tthioisnw s ork werper esented at the 32nd Annual Meeotifn tgh e Societoyf ToxicologyM, arch 14-18,1 993,in New Orleans, LA.
PY - 1993
Y1 - 1993
N2 - Previous studies have shown that the neuronal glycine receptor antagonist, strychnine, mimics the cytoprotective effects of glycine in renal proximal tubules (RPT) (1). The goal of this study was to identify and characterize the site of action of strychnine. 3H-Strychnine bound to RPT in a saturable and reversible manner, and was displaced by unlabelled strychnine (IC50=0.87 mM and a Bmax=57 nmol/mg protein). However, strychnine binding was not inhibited by glycine or related cytoprotective amino acids. Furthermore, the neurotoxicants bicuculline and norharmane, which share the cytoprotective properties of strychnine, inhibited 3H-strychnine binding. These data support the existence of novel low-affinity strychnine binding site on the RPT plasma membrane that prevents toxic cell death.
AB - Previous studies have shown that the neuronal glycine receptor antagonist, strychnine, mimics the cytoprotective effects of glycine in renal proximal tubules (RPT) (1). The goal of this study was to identify and characterize the site of action of strychnine. 3H-Strychnine bound to RPT in a saturable and reversible manner, and was displaced by unlabelled strychnine (IC50=0.87 mM and a Bmax=57 nmol/mg protein). However, strychnine binding was not inhibited by glycine or related cytoprotective amino acids. Furthermore, the neurotoxicants bicuculline and norharmane, which share the cytoprotective properties of strychnine, inhibited 3H-strychnine binding. These data support the existence of novel low-affinity strychnine binding site on the RPT plasma membrane that prevents toxic cell death.
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U2 - 10.1016/0024-3205(93)90538-E
DO - 10.1016/0024-3205(93)90538-E
M3 - Article
C2 - 8412477
AN - SCOPUS:0027259313
SN - 0024-3205
VL - 53
SP - 1203
EP - 1209
JO - Life Sciences
JF - Life Sciences
IS - 15
ER -