Effects of methionyl-tyrosyl-lysine on neurones in the rat central nervous system.

1 The effects of microiontophoretically applied methionyl-tyrosyl-lysine (Met-Tyr-Lys) were studied on single neurones in several brain regions of rats anaesthetized with urethane. 2 Met-Tyr-Lys inhibited 13.5%-25% of neurones in the spinal cord, cerebellar cortex, thalamus and hippocampal formation. No significant inhibitory effects were seen in the cerebral cortex. 3 Additionally, Met-Tyr-Lys excited some cells in the Purkinje cell body layer of the cerebellar cortex (11%) and in the pyramidal cell body layer of the hippocampus and granule cell body layer of the dentate gyrus within the hippocampal formation (17.5%). 4 Both excitatory and inhibitory effects of Met-Tyr-Lys were dose-dependent, of similar rapid time course and were observed both on spontaneously active cells and cells induced to fire by continuous iontophoretic application of DL-homocysteic acid. 5 The possibility that Met-Tyr-Lys might be a novel inhibitory neurotransmitter in both spinal and supraspinal regions of the mammalian CNS is discussed.