Evidence in favour of glutamate as a mediator of synaptic transmission

A microiontophoretic investigation of neurones in the spinal cord, cuneate nucleus, thalamus and cerebral cortex in the anaesthetized cat indicated that glutamic acid diethyl ester (GDEE), α-methyl-glutamate (αMG) and DL-methionine-DL-sulphoximine (MSO) could reversibiy. block, and glutamic acid dimethyl ester (GDME) and para-chloromercuriphenylsulphonate (pCMS) could enhance the excitation of neurones produced by glutamate and by orthodromic nerve stimulation. The action of GDEE was relatively specific in that it was possible to block glutamate-induced excitations without appreciably reducing the sensitivity of neurones to L-aspartate (Asp), L-cysteate (Cys), DL-homocysteate (DLH) and acetylcholine (ACh), whereas αMG and MSO showed no specificity of action and antagonized the excitatory effects of all the amino acids to the same extent. GDME and pCMS enhanced the action of glutamate and aspartate to a greater extent than that of DLH. The responses of neurones in the spinal cord and thalamus to electrical stimulation of branches of the sciatic nerve and of cuneate neurones to dorsal column stimulation were blocked by GDEE and enhanced by GDME in the same manner as glutamate responses. GDEE blocked the responses of cortical neurones to glutamate and thalamic stimulation but the depressant effect was not as commonly observed as in other areas. Studies on the uptake of labelled glutamate into crude synaptosomal preparations of rat cerebral cortex confirmed the existence of a high and low affinity uptake mechanism for glutamate and showed that GDME inhibits the high affinity uptake system. Glutamate and GDEE, but not αMG, enhanced the release of labelled glutamate from slices of rat cortex. No competition between glutamate and GDEE was observed in this system. αMG was found to block the responses of the abdominal stretch receptor organ of the crayfish to applied glutamate. GDEE blocked the- responses of the closer muscle in the claw to electrical stimulation of the excitatory nerve to this muscle.Medicine, Faculty ofCellular and Physiological Sciences, Department ofGraduat