A putative cytoprotective receptor in the kidney: relation to the neuronal strychnine-sensitive glycine receptor

The neutral amino acid glycine has been demonstrated to prevent cell death in numerous cell types exposed to a variety of toxic insults. Recently, the central nervous system (CNS) glycine antagonist strychnine was demonstrated to bind specifically to the plasma membrane of renal proximal tubules (RPT) and mimic glycine cytoprotection. Further, it has been demonstrated in RPT that glycine and strychnine block chloride influx in the late stages of cell injury. The aim of this study was to determine if the RPT cytoprotective site is related to neuronal glycine receptors. Only antagonists to the CNS strychnine-sensitive glycine receptor (strychnine, brucine), and not antagonists to the glycine modulatory site of the NMDA receptor (DCQX, 7-CKA, HA-966) or the GABAA receptor (bicuculline methiodide, picrotoxin), prevented mitochondrial inhibitor (antimycin A)-induced RPT cell death. Using immunoblot analysis, proteins corresponding to the 58 kDa beta-subunit of the strychnine-sensitive glycine receptor and the associated protein gephyrin were identified in rabbit kidney cortical membrane fractions and RPT. No protein corresponding to the 48 kDa alpha-subunit was identified. Thus, glycine and strychnine may exert their cytoprotective effects via a putative plasma membrane receptor that is related to the strychnine-sensitive glycine receptor found in the CNS.