NO-NMDA Receptor Interactions: A Neuromolecular Approach to Novel Therapeutics

Abstract

In recent years, as endogenous sources of oxidizing and reducing agents have been discovered, redox modulation of protein function has been recognized as an important mechanism for many cell types. For our purposes, we will confine our review of redox modulation to covalent modification of sulfhydryl (thiol) groups on protein cysteine residues. If they possess a sufficient redox potential, oxidizing agents can react to form adducts on single sulfhydryl groups or, if two free sulfhydryl groups are vicinal (in close proximity), disulfide bonds may possibly be formed. Reducing agents can regenerate free sulfhydryl (—SH) groups by donating electron(s). Considering endogenous redox agents, in addition to the usual suspects including glutathione, ascorbate, vitamin E, lipoic acid, and reactive oxygen species, nitric oxide and its redox-related species have recently come to the fore. This has occurred largely because of the rediscovery and application to biological systems of work from the early part of this century showing the organic synthesis of nitrosothiols (RS-NO) (reviewed by Stamler et al. 1992). NO group donors represent different redox-related species of the NO group, each with its own distinctive chemistry, which lead to entirely different biological effects.