GLUTAMATE STIMULATION OF TYROSINE-HYDROXYLASE IS MEDIATED BY NMDA RECEPTORS IN THE RAT STRIATUM

We have studied the action of glutamate on striatal tyrosine hydroxylase activity and determined which type of glutamate receptors are involved. Glutamate stimulated (EC50 = 4 +/- 2-mu-M) the activity of tyrosine hydroxylase in slices of rat neostriatum. The selective N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate (10-mu-M) blocked the stimulation; however, both the non-NMDA receptor antagonist glutamate diethyl ester (10-mu-M) and the general excitatory amino acid antagonist kynurenate (10-mu-M) had no effect. NMDA was even more potent than glutamate in stimulating tyrosine hydroxylase activity. Quisqualate (100-mu-M) only slightly stimulated the enzyme, and kainate had practically no effect. Omission of Mg2+ from the incubation medium potentiated the glutamate stimulation. Neither tetrodotoxin nor atropine prevented the stimulation. These results suggest that glutamate stimulates striatal tyrosine hydroxylase activity via NMDA receptors. The lack of effect of tetrodotoxin and atropine suggests that glutamate acts on NMDA receptors located on the dopaminergic nigrostriatal terminal. The stimulation may involve the entry of Ca2+ into the terminal through the NMDA receptor ionophore, since a Ca2+-free medium or cadmium totally blocked the stimulation of the enzyme by glutamate.