Previous studies from this laboratory have identified in bovine pineal gland a glutamate receptor site with a dissociation equilibrium constant (K(D)) value of 0.534 ?M and a receptor density (B(max)) value of 4.84 pmol/mg protein. This pH- and temperature-dependent binding site showed stereospecificity, was activated by Ca(2+) and displayed affinity for both glutamate receptor agonists and antagonists. The role of this glutamate receptor site was investigated by studying the effects of select glutamate receptor agonists and antagonists and of ?-aminobutyric acid on the basal- and on the norepinephrine-stimulated activity of arylalkylamine N-acetyltransferase in rat pineal glands that were incubated in Dulbecco's Modified Eagle Medium at 37 degrees C for 20 min in an atmosphere of 5% CO(2)/95% O(2). l-Glutamate, l-aspartate and glutamate receptor agonists such as ?-amino-3-hydroxy-5-methylisoxazole-4-propinonic acid and quisqualate were all also potent inhibitors of norepinephrine-induced stimulation of N-acetyltransferase. On the other hand, the known glutamate receptor antagonists such as d-glutamylaminomethylsulphonic acid and ?-d-glutamyltaurine stimulated the basal activity of N-acetyltransferase. Evidence of a high concentration of glutamic acid, the presence of glutamate receptors and the inhibition by glutamate receptor agonists of pineal N-acetyltransferase compel one to speculate that, in addition to its well-known metabolic roles, glutamate may modulate in an unknown fashion the activity of melatonin synthesizing enzyme, and the functions of mammalian pineal glands.