Acidic amino acid binding sites in mammalian neuronal membranes: their characteristics and relationship to synaptic receptors

Abstract

This review summarizes studies designed to label and characterize mammalian synaptic receptors for glutamate, aspartate and related acidic amino acids using in vitro ligand binding techniques. The binding properties of the 3 major ligands employed--L-[3H]glutamate, L-[3H]aspartate and [3H]kainate--are described in terms of their kinetics, the influence of ions, pharmacology, molecular nature, localization and physiological/pharmacological function. In addition, the binding characteristics are described of some new radioligands--[3H]AMPA, L-[3H]cysteine sulphinate, L-[35S]cysteate, D-[3H]aspartate, D,L-[3H]APB, D-[3H]APV and D,L-[3H]APH. Special emphasis is placed on recent findings which allow a unification of the existing binding data, and detailed comparisons are made between binding site characteristics and the known properties of the physiological/pharmacological receptors for acidic amino acids. Through these considerations, a binding site classification is suggested which differentiates 5 different sites. Four of the binding site subtypes are proposed to correspond to the individual receptor classes identified in electrophysiological experiments; thus, A1 = NMDA receptors; A2 = quisqualate receptors; A3 = kainate receptors; A4 = L-APB receptors; the fifth site is proposed to be the recognition site for a Na+-dependent acidic amino acid membrane transport process. An evaluation of investigations designed to elucidate regulatory mechanisms at acidic amino acid binding sites is made; hypotheses such as the Ca2+-activated protease hypothesis of long-term potentiation are assessed in terms of the new binding site/receptor classification scheme, and experiments are suggested which will clarify and expand this exciting area in the future.