ABSTRACT
It has recently been demonstrated that glycine can potentiate several measures of N-methyl-D-aspartate (NMDA)-induced channel opening, including radioligand binding to the PCP receptor. These data suggest that the NMDA/PCP receptor complex may be allosterically modulated by a binding site for glycine. We report here that several other monocarboxylic amino acids enhance NMDA-induced [3H]TCP binding and displace [3H]glycine binding with similar apparent affinities and stereoisomerism. The results are discussed with relation to the structural requirements for compounds to bind to this site.
Subject(s)
Aspartic Acid/analogs & derivatives , Glycine/physiology , Ion Channels/drug effects , Receptors, Neurotransmitter/physiology , Amino Acids/metabolism , Animals , Aspartic Acid/pharmacology , Cerebral Cortex/metabolism , Ion Channels/physiology , N-Methylaspartate , Phencyclidine/analogs & derivatives , Phencyclidine/metabolism , Rats , Receptors, GlycineABSTRACT
In extensively washed preparations of rat cortical membranes, N-methyl-D-aspartate (NMDA) increases the specific binding of [3H]TCP by over 4-fold in a concentration dependent manner (EC50 = 3.1 microM). Glycine (1 microM) potentiates the maximal effect of NMDA by a factor of 1.7. The effect of glycine is concentration dependent (EC50 = 380 nM) and strychnine insensitive. These data are discussed with reference to the recently reported effects of glycine on the NMDA operated cation channel and the relationship between the PCP and NMDA receptors.
