l ‐Proline depolarizes rat spinal motoneurones by an excitatory amino acid antagonist‐sensitive mechanism

1 Isolated spinal cords prepared from neonatal rats were used to examine the effects of L-proline (L-Pro). 2 L-Pro (1-8 mM) depolarized ventral and dorsal roots in a dose-dependent manner with one sixth of the potency of L-glutamate (L-Glu). L-Pro was four times more potent than D-Pro. Prolonged application of L-Pro produced a plateau depolarization of motoneurones with no apparent fade. 3 Omission of calcium ions from the medium potentiated the depolarizing actions of L-Pro, L-Glu and quisqualate. 4 L-Pro was antagonized by concentrations of 2-amino-5-phosphonovalerate (25 microM), gamma-D-glutamylglycine (100 microM) and Mg2+ ions (1 mM) that depressed responses to N-methyl-D-aspartate (NMDA). The NMDA receptor-mediated component of the response to L-Pro was estimated to be 60-70%. 5 These data suggest that L-Pro should be considered as a possible excitatory neurotransmitter and that, because L-Pro is a neutral compound, excitatory amino receptors may not require an agonist to possess two anionic groups and one cationic group.