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

Abstract

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 μm), γ-d-glutamylglycine (100 μm) 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 acid receptors may not require an agonist to possess two anionic groups and one cationic group.