Inhibitory actions of a novel endogenous tripeptide, methyionyl-tyrosyl-lysine, on proprioceptive neurons in the lumbar spinal cord of the cat.
The actions of a tripeptide, methionyl-tyrosyl-lysine (Met-Tyr-Lys), isolated from spinal cord and dorsal root ganglia have been investigated by iontophoretic application to single neurones in the spinal cord of the cat. Met-Tyr-Lys inhibited a group of neurons located mainly in laminae V and VI of the lumbar dorsal horn: excitation was never observed. The inhibition was rapid in onset and was not mimicked by the action of the constituent amino acids. Neurons inhibited by Met-Tyr-Lys received proprioceptive inputs as shown by their excitation or inhibition from stimulation of deep receptors and by their responses to leg or foot movement. Bicuculline and strychnine separately, at doses which antagonized responses to gamma-aminobutyric acid and glycine, respectively, had no or little effect both on responses to Met-Tyr-Lys and on the inhibition evoked in the same neurons by low-intensity (1.5-4T) stimulation of the tibial or common peroneal nerves. Thus receptors for Met-Tyr-Lys are different from those for glycine or gamma-aminobutyrate. In addition it is possible that there is a component of the inhibition evoked by peripheral nerve stimulation which is not mediated by either glycine or gamma-aminobutyrate. Met-Tyr-Lys may have an inhibitory role in relation to proprioception.