Agonistic and Antagonistic Activity of Glutamate Analogs on Neuromuscular Excitation in the Walking Limbs of Lobsters

Forty-six analogs of L-glutamate were tested for activity on muscle fibers in the walking limbs of lobsters. Effects on the membrane potential, input resistance, and amplitude of neurally evoked EPSPs and IPSPs were studied as well as effects on applied L-glutamate. Seventeen of the compounds studied depolarized the muscle fibers in a manner indicative of an agonistic action on receptors in the neuromuscular excitatory membrane. Six analogs selectively reduced the amplitude of evoked EPSPs, and at least three of these (kainic acid, D-glutamate, and D-aspartate) antagonized the excitatory action of applied L-glutamate. Kainic acid was the most potent of the blockers of neuromuscular excitation, but even it was relatively weak since a concentration of 1 mM was required for an apparent effect. Generally those analogs in the L-configuration which possessed activity, had agonistic actions, whereas those in the D-configuration were usually antagonistic. These observations provide pharmacological evidence for the concept that L-glutamate is the transmitter agent which mediates neuromuscular excitation in the walking limbs of lobsters. In addition, our results are consistent with recent studies which indicate that L-aspartate may also function in this neuromuscular excitatory process.