A novel low-affinity strychnine binding site on renal proximal tubules: Role in toxic cell death

Gary W. Miller; Rick G. Schnellmann

doi:10.1016/0024-3205(93)90538-E

A novel low-affinity strychnine binding site on renal proximal tubules: Role in toxic cell death

Gary W. Miller, Rick G. Schnellmann

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

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 B_max=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.

Original language	English (US)
Pages (from-to)	1203-1209
Number of pages	7
Journal	Life Sciences
Volume	53
Issue number	15
DOIs	https://doi.org/10.1016/0024-3205(93)90538-E
State	Published - 1993
Externally published	Yes

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Pharmacology, Toxicology and Pharmaceutics(all)

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10.1016/0024-3205(93)90538-E

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title = "A novel low-affinity strychnine binding site on renal proximal tubules: Role in toxic cell death",

abstract = "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.",

author = "Miller, {Gary W.} and Schnellmann, {Rick G.}",

note = "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.",

year = "1993",

doi = "10.1016/0024-3205(93)90538-E",

language = "English (US)",

volume = "53",

pages = "1203--1209",

journal = "Life Sciences",

issn = "0024-3205",

publisher = "Elsevier Inc.",

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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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A novel low-affinity strychnine binding site on renal proximal tubules: Role in toxic cell death

Abstract

ASJC Scopus subject areas

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