Previous studies have demonstrated that strychnine mimics the cytoprotective effects of glycine (1) and that strychnine binds specifically to renal proximal tubules (RPT) at cytoprotective concentrations (2). The goal of this study was to determine a mechanism by which strychnine and glycine are cytoprotective. Antimycin A (0.1 μM) caused chloride influx subsequent to mitochondrial inhibition and prior to the release of lactate dehydrogenase (LDH) activity (a marker of cell death/lysis). The addition of strychnine or glycine prevented the chloride influx and LDH release. The chloride channel inhibitors ethacrynic acid, furosemide, anthracene-9-carboxylic acid, DIDS, and SITS decreased LDH release in RPT exposed to antimycin A with a rank order of potency of DIDS > ethacrynic acid=furosemide=anthracene-9-carboxylic acid > SITS. These data, in conjuction with the preceeding paper, indicate a critical role for chloride influx in cell death/lysis; support the existence of a novel strychnine binding site on the plasma membrane of RPT that is coupled to a chloride channel; and suggest that glycine and strychnine are cytoprotective through their inhibition of chloride influx.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)