Inhibition of Enkephalin Binding to Opiate Receptors by Zinc Ions: Possible Physiological Importance in the Brain

Abstract

Zn2+ can totally block stereospecific binding of 3H-met-enkephalinamide (2-D-ala-5-L-methionine) to opiate receptor sites in synaptic membranes of the hippocampus, the cerebral cortex and the basal ganglia of the rat brain. Analysis of binding isotherms indicates that this inhibitory effect involves a decrease in both receptor affinity and the number of binding sites. Evidently, Zn2+ reacts with essential SH groups of the opiate receptor. The endogenous concentrations of Zn2+ in the hippocampus, the cerebral cortex and the basal ganglia are compatible with the concentrations needed to inhibit opiate receptor binding in vitro. The hippocampus especially contains a high concentration of Zn2+, which are localized exclusively in the giant boutons of the mossy fibers. The hippocampal distribution of enkephalin and Zn2+ is identical and confined to the mossy fiber zone. Zn2+ may represent important modulators of opiate receptor binding in the CNS, particularly in the hippocampal mossy fiber zone.